The main effectors of apoptosis encompass proteases from the caspase family, which reside as latent precursors in most nucleated animal cells. The apoptotic caspases constitute a minimal two-step signaling pathway. The apical (initiator) caspases are activated within oligomeric signaling complexes in response to apoptotic stimuli. Their mechanism of activation probably results from proximity-induced clustering to the dimeric active forms. Once activated, the apical caspases directly activate the executioner (effector) caspases by limited proteolytic cleavage. The distinct activation mechanisms explain how an apoptotic stimulus is converted to proteolytic activity, and how this activity is amplified to allow for limited proteolysis of the dozens of protein substrates whose cleavage is required for efficient apoptosis.