After an accident on the Enterprise in 2153, a spatial distortion leaves Archer with a puzzling form of amnesia due to interspatial parasites and unable to form new long-term memories. He wakes up every day not remembering anything from the day before. At one point, he is further confused about finding himself in the future aboard an Enterprise commanded by T'Pol. Twelve years into the future, he wakes up one morning and is stunned to learn the outcome of the human-Xindi conflict. After destroying Earth, the Xindi continued searching the galaxy, determined to annihilate all Humans. The remnants of humanity have settled on the distant planet Ceti Alpha V. Now, Archer learns that he may be the key to undoing this entire tragedy if Phlox's new treatment destroys the parasites without harming him.

Trip suffers a catastrophic injury in an accident that disables Enterprise inside a hazardous space cloud. His only hope for survival is a transplant from a clone or "mimetic symbiont" which Phlox grows from one of his exotic creatures. Phlox and the crew named the clone Sim. But his rapid growth and replication of Trip's behavior alarm the crew. Archer faces an ethical dilemma as the clone gains sentience and does not want to die from harvesting his organs for Trip's survival.