Twelve years in the future, Archer finds himself living in a modest home on a desolate planet with T'Pol as his caregiver. The last thing he remembers is walking down a corridor on his way to the Bridge. T'Pol explains that an anomaly hit the ship, and Archer knocked her out of the way of a distortion wave just in time. The wave rendered him unconscious, and when he awoke, Phlox had troubling news: Archer was infected with several clusters of parasites, which prevented him from forming long-term memories. Over the next few months, Phlox searched for a cure, but was unsuccessful — the organisms are from a domain outside of normal space-time, and none of his treatments had any effect. Meanwhile, T'Pol was granted a field commission and promoted to captain. After several months of searching, the crew learned where the Xindi weapon was being constructed — but the Xindi caught wind of it and sent ships to intercept Enterprise. The ensuing battle left Enterprise heavily damaged, and though the crew eventually located the facility where the weapon was being constructed, it had already been launched. Earth was destroyed. T'Pol relates to Archer that the Xindi also managed to destroy every human outpost they could find — only 6,000 humans are left.

After this devastating turn of events, a planet was located for the survivors. T'Pol resigned from Enterprise and went to live there as Archer's caregiver, leaving Trip in command. T'Pol tells Archer that Enterprise is currently in orbit of the planet, patrolling the system. As Archer takes all of this in, he receives a visitor: Phlox. Phlox reveals that he's been on Denobula, researching a cure for Archer's condition. After nearly a decade, he believes that he finally has the technology to destroy the parasites that have crippled Archer. He explains that the procedure requires a great deal of energy, which can only be provided a warp-capable starship: Enterprise.

Onboard the battle-scarred ship, Archer experiences an emotional reunion with his former crew. Trip has been in command for nearly a decade, while Reed has just been promoted, and will be taking over the starship Intrepid. After catching up with his old crew, Archer joins T'Pol and Phlox in Engineering, where they prepare for the first step of the operation. After removing the first cluster of parasites, they notice a surprising discrepancy: the parasites have disappeared from all of Phlox's scans, even the ones taken 12 years ago. T'Pol and Phlox realize that if they eliminate all the parasites, they could undo the events of the past 12 years, altering history and possibly saving Earth and humanity.

Unfortunately, Enterprise has other problems: the Xindi have tracked down the humans and are fast approaching. Trip insists that he can't spare any of the ship's power for Archer's operation — he needs it all to fend of the Xindi. T'Pol, however, knows that the key to saving humanity is to eliminate the parasites once and for all. As Enterprise is attacked from all sides, she and Phlox head to Engineering to complete the operation. Unfortunately, their equipment has been damaged in the battle. Archer, however, remembers Phlox saying that the parasites could be destroyed by a subspace implosion and suggests they try to create one. T'Pol notes that they will need to overload three plasma injectors to do so. It will destroy the ship, but it may be their only shot. As the trio works to create the implosion, the Xindi board Enterprise and continue to attack. Phlox and T'Pol are both killed, but Archer manages to ignite the implosion. As Enterprise erupts in a massive antimatter annihilation, Archer and the rest of the crew suddenly find themselves 12 years in the past with no memories of what has transpired. The parasites have been eliminated — Archer has been injured by the distortion wave, but will recover. T'Pol visits Archer in Sickbay and chastises him for putting himself in danger in order to save her. Still, the captain can see that she's grateful. As she leaves, Archer can't help but tell her — half-jokingly — that she would make a great nurse.