The elimination of cells by programmed cell death is a fundamental event in development where multicellular organisms regulate cell numbers or eliminate cells that are functionally redundant or potentially detrimental to the organism. The evolutionary conservation of the biochemical and genetic regulation of programmed cell death across species has allowed the genetic pathways of programmed cell death determined in lower species, such as the nematode Caenorhabditis elegans and the fruitfly Drosophila melanogaster to act as models to delineate the genetics and regulation of cell death in mammalian cells. These studies have identified cell autonomous and non-autonomous mechanisms that regulate of cell death and reveal that developmental cell death can either be a pre-determined cell fate or the consequence of insufficient cell interactions that normally promote cell survival.