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Regeneration was devised as a way of defeating death. In order to prolong life, a Time Lord should only regenerate at the point of death. However, in the Target novelisation "Doctor Who and the Deadly Assassin" (novelisation of "The Deadly Assassin") it is stated that the reason The Master has used up his twelve regenerations (while the Doctor has only used three) is because he deliberately regenerated to change his appearance for his various schemes. "Nightmare in Silver" has the Doctor state that he can regenerate at will, too, though it's implied that this might have been a bluff.

It is also unclear what caused Romana to regenerate at the start of "Destiny of the Daleks", and this may have been deliberate on her part. Various spin-off media have suggested different reasons for her regeneration.

In "The Twin Dilemma", the Time Lord Azmael voluntarily induced a regeneration. Since he had already regenerated 12 times & was in his final incarnation, this killed him. (It also killed Mestor, who had taken posession of Azmael's body, & that was why Azmael chose to commit suicide in this way.)