Mechanisms of regulated or programmed cell death (PCD) are essential for development and maintenance among metazoans. PCD itself can occur via a number of distinct mechanisms, and the consequential subcategorization has given rise to an array of terminology, including: apoptosis (caspase dependent or independent), apoptosis-like PCD, necrosis, necrosis-like PCD, accidental necrosis, autophagic cell death and mitotic catastrophe. The completion of genomic sequencing projects has convincingly revealed that a dramatic increase in the complexity of at least one family of proteins involved in apoptosis, the caspases, arose with multicellularity (Aravind et al., 2001). However, data from a wide range of single-celled organisms, both pro- and eukaryotic, suggest that important components of PCD and apoptotic pathways have ancient origins (Koonin and Aravind, 2002). For example, so-called ‘apoptosis domains’ are prevalent in a number of unicellular organisms, including bacteria, and a central role for the mitochondria in apoptosis has been highly conserved among eukaryotes. This has led to the suggestion that some mechanisms of apoptosis arose from early prokaryotic host/pathogen relationships, an example of this being the capture, and ‘taming’, of a pathogenic mitochondrial precursor (Ameisen, 2002). Such a theory proposes that the prokaryotic mitochondrial precursor, widely believed to have been a proteobacterium, had evolved to possess a battery of molecules capable of killing its host. Under conditions whereby the host environment was no longer desirable, for example, starvation, the invading organism could release an arsenal capable of destroying the parasitized organism. In order to avoid such a fate the host cell would have to develop ways of suppressing this programme of cell death, while maintaining the pathogenic mitochondrial precursor and it's valuable metabolic potential. Evidence to support such a theory comes from the fact that factors secreted or associated with the mitochondria, such as cytochrome c, HtrA/OMI and apoptosis-inducing factor (AIF), have been found to play a role in apoptosis that is conserved throughout the eukaryotes. Another weapon employed by the pathogen may have been the production and release of damaging reactive oxygen species (ROS) via a membrane bound electron transport system. Again, ROS production by the mitochondria is central to a broad range of apoptotic mechanisms throughout eukaryotes. The hypothesis that subsequent appropriation of the pathogen followed by its adaption to participate in programmed and regulated suicide provides a tantalizing hypothesis as to the origins of the apoptotic machinery. The discovery that the model eukaryote Saccharomyces cerevisiae can undergo apoptosis allows us to examine such a hypothesis in more detail. For example, is the ability to undergo apoptosis beneficial to a unicellular organism, or does it simply represent an inability to suppress the mitochondria's latent killer instinct? To address this we must first understand the molecules involved, then identify physiologically relevant pathways that regulate their use. Finally, we must reveal circumstances under which apoptosis becomes beneficial to the organism involved.