After Adric's tragic death, the Doctor met a new companion, an alien boy stranded on Earth by the name of Vislor Turlough, he did not know that Turlough had been commissioned by the Black Guardian to kill him out of revenge for the Key to Time affair. Soon after,Nyssa left to help cure Lazar's Disease, the Doctor met entities known as Eternals racing in yacht-like spacecraft for the prize of "Enlightenment." Turlough won the prize and used it to break free from the Black Guardian's influence.

The Doctor and his companions then met three of his previous incarnations when they were summoned to the Death Zone on Gallifrey by President Borusa, who was attempting to gain Rassilon's secret of immortality. After defeating Borusa, the doctor was again declared President and, again, he fled his responsibilities. After many more adventures, both Tegan and Turlough left the TARDIS. Tegan would find the death and violence they encountered on their travels too much to bear, and Turlough returned to his home planet of Trion.

Ultimately, the Fifth Doctor and his last companion Peri Brown, a buxom American botany student, were exposed to toxic levels of the drug spectrox on Androzani Minor. After securing the antidote in the midst of a bloodbath between government forces, gunrunners androids and corrupt business men, he barely managed to carry the unconcious Peri back to the TARDIS. Unfortunately, he spilled some of the antidote. He gave what was left to Peri, even though he knew the poison might prevent his regeneration, sacrificing his life for hers...