After a tactical group infiltrates the DSR and steals Rambaldi artifacts, CIA director Hayden Chase discovers that the alarms at the DSR were disabled from Nadia's computer, allowing the raid to happen, and shows up at the apartment to question her. Soon Sloane and Jack arrive and suspect that Sophia, who had access to the computer while she was living with Syd and Nadia, is Elena Derevko. They follow her trail to a dead Rambaldi follower, a stunning betrayal, and a presumed dead family member...
Rambaldi's catastrophic endgame begins to fall into place as a giant version of the Circumference/Mueller device is found floating over city in Russia, driving the citizens made. After a wounded Dixon reveals that Irina is alive, Sydney, Nadia, and Jack set off to find her. Irina had been captured, and then duplicated using Project Helix, in order to give the impression that she was dead. Sydney and Nadia discover Irina is being held inside a camp in Tikal, safely in the clutches of Elena's army. Irina had apparently been working to counter Elena's organization, the Covenant, and actually PREVENT the Rambaldi endgame. Irina tells of a page she destroyed, a page that was key to Rambaldi's endgame. Under torture, she finally broke and recreated it for Elena. After a short respite, the transport turns towards Russia, and Sydney, Vaughn, Jack, Nadia, and Irina parachute down, towards Elena, Sloane, the Circumference....and destiny.
As Eric prepares to go to Africa, Kitty is still having problems dealing with his departure. Donna is also having problems; she can't come up with an appropriate going away gift, but some advice from Kitty puts her on the right track. Charlie accidentally sees Kitty naked, and his attempts at apologizing only make things worse. Jackie is still in Point Place after telling everyone she was leaving for Chicago; her attempts to give Hyde one last ~last~ chance don't quite go the way she hopes they would.
Kelso drops Jackie off in Chicago, but she is immediately homesick and reaches out to the gang for companionship. Eric finds out at the last minute that Kitty deliberately hid a letter outlining the vaccination shots he’s required to have before going to Africa for the year. He has his final Circle with the guys only to finally be busted by Red! As Eric says his good-byes to everyone, Hyde talks to Leo about his true feelings for Jackie and decides to follow her to Chicago…with disastrous results.
The French woman-Danielle Rousseau-shocks the survivors by showing up to the camp with a dire warning about "the Others" who are on the island, and the black smoke that precedes them. Meanwhile, Michael and Jin ready the raft for sailing. In flashbacks, we see the survivors final moments before they boarded their fateful flight.
After a nightmare, Clark goes to the cave to confront his father Jor-El. Jor-El warns that the crystals have fallen into human hands and have triggered a new meteor shower which will annihilate the Earth unless he reunites the three crystals. Meanwhile, Lex helps Lana, who has apparently commited murder, but then turns against her to get possession of her Kryptonian stone. As disaster looms, Chloe and Lois try to find Lana while Clark attempts to reassemble the stones, and Jason returns to make things unpleasant for the Kents.
Jay asks Michael to get a vasectomy, but he says no. Eventually he tells Jay that he will go through with it, but then backs out at the last second. Jay says that she will instead get a hysterectomy. After she comes out of the clinic, Michael tells her that he will get the vasectomy, but she then reveals that she is pregnant.
Lorelai rescues Rory after a night of reckless behavior. Shocked to hear her daughter's plans for the future, she turns to Luke for help.
Monica orders her units to turn the streets of Farmington inside-out when two officers mysteriously disappear after answering a 911 call. Shane tries to make amends with his old crew after Vic agrees to help him get out from under Antwon, but things don't work out as planned. Dutch and Claudette convince Monica to let them take active roles in the case of the missing officers, but soon find themselves at a dead end with the only witness being clinically insane.
House must decide whether to take the case of his ex-love's husband and he gives medical students a lecture they'll never forget.
Nathan is released from the hospital and returns home to a pile of unpaid bills and an eviction notice. Lucas, Peyton and Brooke throw a fundraiser Tric to raise money, but Dan is the one that comes to Nathan's rescue. However, his gift comes with strings - he wants Nathan to ask Haley for an annulment.
After careful observation of Professor Avalon, Techna and Digit become convinced that he isn't who he says he is. They begin researching his past and fear he is the Angel of Doom in disguise.
Jim uses all his manipulative skills to get himself out of jail, but will Di realsie he is using her? Everyone on G-Wing is up in arms about the extortion racket Natalie Buxton and her sidekick Darlene Cake are running. Jim blackmails Neil Grayling into giving him the Wing Governor's job, and starts by sacking the two Julies from the kitchen. Phyl and Bev jump at the chance to replace them, but they're unprepared for all the hard work. Sylvia is sure that she has a mysterious illness - Dr Nicholson is unterested until a letter arrives for Sylvia...!
After a woman's head is found in a car junkyard, the detectives track it down to the black market.
George steps in to be Jason's sports agent when NFL Quarterbacks Daunte Culpepper and Donovan McNabb (guest starring as themselves) pay a visit to the Lopez household to draft Jason for their alma maters and a minor league baseball recruiter approaches him for a contract. Meanwhile, Carmen and Los Lobos guitarist Cesar Rosas stir things up at George's family birthday bash.
Michael buys an R.V. and the family heads to the Grand Canyon for a vacation.
Gigi is pulled out of her depression when a call from her agent brings news of a job – a gig for a cable network movie shooting in the Rockies. Not realizing she is merely the movie’s required Canadian content, Gigi ventures north in search of a break from Los Angeles and her ex-boyfriend Payne. Her wish comes true when she meets (and beds) Bo, the Olympic bobsledder – only to find out later he’s an anti-Semite.
In the hopes of getting closer to Phyllis, Dee Dee sets her up with her bitter divorced professor. However, the relationship soon fizzles, and the professor seeks revenge against Phyllis by turning her in for having too many cats. Phyllis blames Dee Dee, whose efforts to correct the situation only wind up making it worse.
In 1996 a beautiful newlywed, was attacked and left for dead. The only thing taken was her wedding ring and she has been in a coma ever since. The man jailed for the crime is now a born-again Christian and is protesting his innocence
Ephram prepares to leave for Europe as he feels that he has nothing left for him in Everwood. However, he's caught off-guard and questions his plans when Andy reveals the secret that Amy has been keeping from Ephram. Meanwhile, Nina and Jake contemplate going into business together, but the stress on their relationship proves a big obstacle to overcome. Meanwhile, Bright finally confesses he has feelings for Hannah.