T'Pol must save the ship after the crew becomes obsessed with trivialities during the approach to a black hole.

After receiving a warning about a radioactive storm approaching Enterprise, the crew is forced to take shelter in the ship's catwalk.

Enterprise is held captive by non-corporeal beings who claim to be explorers.

Mayweather temporarily leaves Enterprise to visit the cargo ship Horizon, where he was born and raised. Meanwhile, the Enterprise crew observes an unusual planetary event.

At Dr. Phlox's request, Enterprise attempts to retrieve 3 Denobulan scientists from the planet Xantoras, where the Goverment has ordered all off-worlders to evacuate within 3 days. Tucker, Reed, and Mayweather navigate a series of labyrinthine underground caves in search of the scientists. Meanwhile, Enterprise lends assistance to a damaged ship fleeing the planet. Doctor Phlox faces an ethical dilemma when one of the refugees of the ship refuses life-saving treatment. The patient, an Antaran, holds a grudge against Phlox stemming from a war between their races that ended 300 years ago and would rather die than be treated by a Denobulan. Phlox defies Archer's direct order to force treatment because it goes against the Deobulan code to yield to "the will of the patient."

Enterprise encounters a hyper-giant star. While there, they make first contact with the Vissians, a technologically sophisticated race with three genders. While making quick friends, and eagerly learning about the advanced technology, Trip gets curious about the Vissians third gender, known as the Cogenitor, who is crucial in the Vissian reproductive process. Against the wishes of the Vissians, Trip befriends the Cogenitor and encourages it to defy its cultural boundaries, which the Vissians are made aware of, and are angered by.

An alien probe launches a devastating attack on Earth. Archer, still being hunted by the Klingons, brings the Enterprise back home to investigate.

Enterprise follows a lead and discovers a Xindi lab that refines Kemocite, the key ingredient in the weapon being built to destroy Earth. An away team of Archer, Reed and Hayes confront the lead researcher, Gralik Durr, who was employed by Degra to refine the Kemocite but was never told what it would be used for. When Gralik realizes it was his research that contributed to the 7 million deaths on Earth, he agrees to help Archer prevent further loss of life. Meanwhile, on Enterprise, Phlox and Tucker study the weapon they seized from the Xindi and find an organic component, a life-form serving as the rifle's power cell. Despite T'Pol's objection, Tucker tests the weapon.

His memory crippled, Archer awakens years in the future, after the Xindi have reduced Earth to a cinder and the remnants of humanity have settled on a distant planet. Now, Archer learns that he may be the key to undoing this tragedy.

Enterprise investigates a previously unknown colony of humans who are living in the fashion of the American Old West. They are oppressing an alien race called the Skagarans.

Enterprise is taken over by religious zealots who want to use the ship in a war against heretics.

After a bombing destroyed the Earth embassy on Vulcan, a group known as the Syrrannites are suspected. T'Pol receives a map from her Syrrannite mother, leading into a dangerous desert, the Forge.

While Enterprise tries to bring Trip on board to reverse the malicious Klingon modifications, Phlox and Antaak find a cure for the virus that will not please General K'Vagh.