Apoptosis represents a crucial process in modulating organ development in the embryo, in organ homeostasis in the adult, and in fostering appropriate immunological function. Caspases represent two central class of molecules that are either involved with the stimulation of the apoptotic cascade (initiator caspases), or the various sequential biological pathways required for its execution (effector caspases). With an eye towards therapeutic opportunities, this review discusses in detail the lineage of initiator and effector caspases, how they are each activated, their substrates, their regulation, and maps out how they interact throughout the process from initiation of the first apoptotic signal to the final consequential breakdown of cellular integrity.