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Apoptosis is co-ordinated by a family of cysteine proteases, the caspases, that dismantle the cell by targeting a panoply of proteins for limited proteolysis. The mammalian caspase family contains 14 members, a subset of which participates in apoptosis, with the remainder likely to be involved in the processing of pro-inflammatory cytokines. Apical caspase activation events are typically initiated by adaptor molecules that promote caspase aggregation and facilitate caspase autoactivation. In contrast, distal caspase activation events are controlled by caspases activated earlier in the cascade. Many cellular stresses provoke apoptosis by damaging mitochondria which results in the release of factors [such as cytochrome c and SMAC (second mitochondrial-derived activator of caspase)/Diablo] that trigger caspase activation and cell death. Here, we discuss the hierarchical nature of the caspase cascade that is triggered upon the release of mitochondrial cytochrome c into the cytoplasm, and the role of specific caspases within this cascade in targeting proteins for degradation. Finally, feedback amplification loops and important control points within the caspase cascade will be discussed.