Since Then: Desmond's mind traveled back in time and saw Charlie performing on a London street corner. He began experiencing premonitions of Charlie dying and repeatedly saved his life. He was present when Charlie died. In the afterlife, Charlie helped guide Desmond toward awakening.
Origin: On reurning from his failed sail from the Island, Desmond talked to Claire on the beach about her baby its father.
Since Then: Desmond later moved into the beach camp. He built a lightning rod above Claire's tent, saving it from a lightning strike, and he later saved her from drowning in the ocean. Some time later, he interrupted her attempts at catching a bird for a rescue message, but he later caught one for her himself. He mentioned Claire to Charlie to try to dissuade him from killing himself in the Looking Glass, but to no avail.
Desmond escaped the Island, and he later returned and left again without seeing Claire. The two may or may not have ever met again when alive. After death though, in a flash sideways, Desmond approached Claire in LA airport, offering her a ride and suggesting her unborn child was a boy. He later approached her again and brought her to his lawyer to introduce her to Jack. This didn't wake her up, but she ended up at a concert, and Desmond brought Kate to her table. Soon after she gave birth to Aaron and woke up, Desmond appeared and told them the next steps toward moving on.
Origin: The two met several times over the course of their lives and afterwards, but each time, at least one did not recognize the other.
Since Then: Desmond's first contact with Daniel happened after his mind traveled from 1996 to 2004. He spoke to Daniel over a phone, and his mind then traveled back to 1996, leading to the pair's first chronological meeting. Desmond gave Daniel instructions that he'd heard from the scientist himself in 2004, helping Faraday perfect his machine for sending minds through time. Daniel then advised Desmond about the concept of constants, saving the man from death by temporal displacement.
Desmond forgot the experience, and he ended up on the Island, where he was shocked one day to find Daniel knocking on the door of the Swan. This time, Daniel was the one time traveling, and he soon vanished. Desmond showed no recollection of this meeting for years to come, and when Daniel came to the island in December of 2004, the two met as strangers. Daniel himself had forgotten their 1996 meeting due to brain damage.
Faraday guided Desmond by phone when the man became mentally unstuck in time, and he later discovered to his surprise a note in his journal about Desmond's importance. When Daniel himself became physically unstuck in time, he sought Desmond's help, leading to their meeting at the Swan.
Desmond finally recalled this encounter in 2007, and he followed Daniel's instruction to seek out the man's mother. He learned, in the process, details of Daniel's questionable experiments. The mission ultimately sent him into Charles Widmore's hands and back to the Island.
After death, the two met, and Daniel advised Desmond, sending him towards Penny. The two spoke of a common bond they knew nothing about while alive: Penny, Desmond's eventual wife, was Daniel's half-sister.
Origin: Eloise saw Desmond's name in her son's journal
Since Then: Eloise followed Desmond for some of his life. She was in contact with Brother Campbell, who discouraged Desmond from becoming a monk. Then when Desmond entered Eloise's jewelry shop to buy an engagement ring, she told him not to, telling him his destiny lay on the Island. He bought the ring, but eventually heeded her words. Years later, he remembered Daniel telling him to meet his mother, though Desmond didn't realize he'd already met the woman. He visited her and angrily left. Eloise later visited Desmond in the hospital. In the afterlife, Eloise again tried to convince Desmond to give up his mission. This time, he ignored her completely.
Origin: The two got to know each other following the Swan implosion. Hurley lent a shirt to a naked Desmond in the jungle.
Since Then: Hurley was the first to notice Desmond's premonitions, and he successfully got Desmond to reveal the truth behind them. The two mourned together after Charlie's death. Both escaped the island but returned, and once Hurley became protector of the island, he planned to help Desmond return home. In the flash sideways, Desmond helped wake Hurley up. The two then worked together to wake their other friends.
Since Then: Desmond and Ilana never knew each other while alive. Though Ilana trained her whole life to protect the candidates, Jacob evidently told her nothing of Desmond, his backup in case she failed. Despite never knowing her, Desmond greeted Ilana as an old friend in the flash sideways.
Since Then: The two first ran into each other at a stadium in Los Angeles, and they met again on the Island. They escaped the island together, and Jack warned him as they parted to beware of Widmore. When Desmond returned to the Island, Jack, now the Island's protector, led him to the Heart. Desmond descended, telling Jack he would go somewhere else where they could be with their loved ones. He was wrong, and Jack helped him escape from the Heart. They met again on a plane in a flash sideways, and they hugged before they moved on together.
Origin: The two shared a line for coffee. Desmond lacked American currency to pay the bill, and Libby offered to cover it.
Since Then: Desmond jokingly asked for a further $42,000, and when Libby pressed him for details, he explained he needed a boat for Widmore's race. Libby lent him one her late husband gave her. Desmond set sail, and the two never met again while alive, though both coincidentally ended up on the Island for a period years later. Desmond tried to escape it in Libby's boat, and he returned just as the survivors were holding her funeral. After death, Desmond helped connect Libby with Hurley, and he watched from afar as they kissed.
Origin: Each unknowingly restored the other's faith. Locke, after Boone's accident and his own temporary paralysis, banged at the Hatch, desperate for answers. Desmond, inside, turned the light on, renewing Locke's sense of purpose. Desmond, meanwhile feared the world was "all gone" and planned to kill himself, which may have indeed destroyed the world. Locke's banging convinced him that life remained.
Since Then: Locke later entered the Hatch, and Desmond turned on him with a gun. Locke introduced himself and described Kate as the larger threat. Desmond explained the station's purpose to John but fled when the computer appeared to break. He returned a few weeks later and laughingly greeted the "box man". The two conspired to lock others from the Swan and let the countdown timer reach zero. Desmond changed his mind at the end, turning the fail-safe. He later experienced a premonition of Locke giving a speech, and he joined Locke in pursuing Eko. Locke later left the camp, supposedly to rescue Jack, and he died before they met again. Desmond left the Island and returned, and a man who appeared to be John Locke unexpectedly threw him in a well. Hurley or Ben likely later explained the man's identity. After death, Desmond ran Locke over with his car in an attempt to "awaken" him. ("Everybody Loves Hugo")
Origin: On the day Desmond was relieved of his duties as an apprenticed monk at the monastery, Desmond met Penelope picking up a shipment of wine.
Since Then: The two dated, and Penny moved in with him. After two years together, Desmond decided to marry her, but her father rejected his request. He bought a ring nonetheless, but the jewelers insistence that his destiny led elsewhere convinced him to break up with Penny. He joined the army and was dishonorably discharged, and Widmore gave Penny none of the letters Desmond wrote Penny. After his release, Desmond entered a race around the world, despite Penny's objections, and ended up on the Island, where a letter she had tucked into his book saved him from killing himself. Penny, meanwhile, searched the world for him, eventually uncovering the Island's location. Desmond became unstuck in time trying to escape the Island, and contacting Penny again saved him. Penny then managed to rescue him in her boat. The two married and had a son. The Island separated them once more, but Hurley later planned to send him home. In the afterlife, Desmond met Penny again, spurring his mission to wake up his friends. They later moved on together, along with their friends.
Origin: For six years, Desmond dated Ruth, a local girl.
Since Then: The week prior to their wedding, he left her due to wedding jitters and joined a monastery in Eddington, Scotland. On the day Desmond was relieved of his duties as an apprenticed monk at the monastery, Desmond meets Penelope where she's picking up a shipment of wine to deliver to Carlisle.
Origin: Sawyer saw Desmond aboard the Elizabeth when its arrival interrupted a funeral.
Since Then: Sawyer and Desmond barely interacted during the series. Sawyer was away when the survivors first met him in the Swan. Soon after his return, Sawyer again left the camp, now kidnapped by the Others. Sawyer returned, and the two spent about a week in the same camp, and Desmond helped Sawyer hunt a boar to share with the survivors. When Desmond returned from his and Charlie's Looking Glass mission, James heard Desmond deliver the news. Sawyer then joined Locke's camp, and Desmond flew to the freighter, and the two didn't meet again till the series finale. Sawyer went to a well to try and save Desmond but found the man already gone. The two later walked to the Heart of the Island together.
In a flash sideways, Desmond turned himself in to Sawyer after running over Locke.
Origin: Kate asked Sayid to fix Desmond's computer. He did so, asking few questions.
Since Then: Desmond tried to sail away but returned after a few weeks. He gladly gave Sayid his boat for a mission, thinking escape now impossible. The two later flew to the freighter together, where Sayid helped Desmond overcome his temporal displacement. They boarded the helicopter again to leave it, and Penny's boat rescued them after it crashed. Years later, both returned to the island, and Desmond convinced Sayid to reject the Man in Black. Right before he died, Sayid told Jack how to find Desmond, thinking Jack the next protector.
After death, Desmond helped Sayid escape police custody, sending him to Hurley to help awaken him.
Origin: Desmond asked for permission from Widmore to marry his daughter, and he refused, even greatly demeaning him.
Prize: Penny's wishes
Fuel: Desmond asked for permission to marry Penny, but while Widmore admitted it was noble gesture and pulled out a very expensive bottle of MacCutcheon whiskey and says that unlike himself and the whiskey's maker, he is not a great man. Since Desmond is not worthy of drinking his whiskey, he is not worthy of marrying his daughter. ("Flashes Before Your Eyes") Desmond goes to Widmore at a auction and asks for Penny's number, which Widmore gladly gave to him since Desmond was a coward and his daughter now hated him. ("The Constant") After Desmond got out of prison, Widmore waited in his limo outside of the compound and offered Desmond a ride. Desmond reluctantly did. Widmore presented Desmond with 2 boxes, one containing all the letters he had written to Penny over the years, and the other contained an extremely large sum of money. Desmond refuses to take the money, despite what Widmore thought he would do since he was a coward. Desmond later participates in Widmore's race around the world in order to show him how honorable he is and win back Penny's heart, but Desmond instead gets lost at sea and crashes on the Island. ("Live Together, Die Alone, Part 1") Desmond later makes it off of the Island with the Oceanic 6, and Jack warns Desmond to not let Widmore find him. ("There's No Place Like Home, Part 2")
Resolved: Yes. Later Desmond finally married Penny and Widmore has urged them both to keep themselves hidden because of the war with Ben. ("Jughead") However Widmore kipnapped Desmond and brought him back to the island against his will but also told him he was sorry for doing so after he was attack by him for doing what he did. He then unleased a huge amount of electromagnetism on Desmond to see if he could survive, hoping Desmond would venture, as he successfully did, into The Heart of the Island and stop the Man in Black from destroying it and escaping. As proven in the flash-sideways timeline, now known to be the Afterlife, Desmond and Charles Widmore seemed to have a very good working relationship, symbolizing that each were able to accept their differences and "move on."