About 2.2 billion years ago, as the oxygen levels on the planet were rising, a new sort of life-form emerged, forged from a shaky alliance of what were to become the mitochondria and the remainder of the cell. The protomitochondria brought respiration to the partnership, and with it the power to kill the new cell through the production of reactive oxygen species, a mechanism of cell death that still exists throughout the eukaryotes. However, it was about 1.5 billion years later, as multicellular animals emerged, that our story probably begins. Apoptosis has now evolved as a physiological cell death in response to environmental and developmental signals, a complex decision-making system with the mitochondria at its heart. Apoptotic cell death is found throughout the animal kingdom, and it culminates in the execution, packaging, and disposal of the dying cells.

Several recent advances have contributed to an emerging (and evolving) view of how apoptosis proceeds once initiated, to the point that we can speculate on a pathway for this remarkable process. This is a pathway, however, that may differ in interesting ways between different types of animals. This review will focus predominantly and “phylocentrically” on the apoptotic pathway of the chordates, but will draw parallels to other phyla.