Mitochondria are key players in fundamental processes such as energy production and adaptive responses to cellular stress, including apoptosis. Mitochondrial membranes may undergo permeabilization when perturbed by a number of intracellular stress mediators, and consequently may allow the release of intramitochondrial proteins. This event triggers and amplifies the cellular apoptotic program, provided sufficient energy is available. Mitochondrial membranes are therefore both targets and regulators of intracellular pathways controlling cell fate. Evidence is emerging that the integration and biological outcome of these pathways might be critically dependent on the unique lipid composition of mitochondrial membranes.