Fifteen years of apoptosis research have led to the widely accepted idea that the major form of programmed cell death in mammals proceeds via the mitochondria, and that mitochondrial control of apoptosis is regulated by a specialized family of proteins known as the Bcl-2 family. Here we will consider some very recent data that has shed new insight into the regulation of these proteins and the impact of mitochondrial dynamics on mitochondrial outer membrane permeabilization (MOMP) and apoptosis.