Several stimuli that trigger apoptosis seem to do so by inducing activation of proteolytic enzymes—
in particular, but not exclusively, caspases. In order to activate initiator caspases, several molecules
of caspase zymogens have to be brought to close proximity to allow self-processing thanks to the
moderate catalytic activity of the zymogens. This is achieved through specific adaptor proteins that
facilitate the recruitment of initiator caspases into large complexes. Activated upstream caspases
then initiate a proteolytic cascade culminating in activation of effector caspases, degradation of
cellular substrates, and cell death. Here, we describe the main signaling pathways that promote
initiator caspase activation and apoptosis following a variety of stimuli.