Significant advances have been made in the study of mechanisms by which apoptosis regulates immune function. One area receiving renewed attention is killing of target cells by cytotoxic T lymphocytes (CTL) and natural killer (NK) cells. A new perspective suggests that granzyme B enters cells via receptor-mediated endocytosis, after which it can act via mitochondrial disruption to trigger apoptotic pathways. The study of intracellular mechanisms driving lymphocyte death also saw major advances as the Bcl-2 family of proteins continues to grow in number and complexity. In addition, the intricacies of the mitochondrial role in apoptosis are starting to unravel with reports of novel proteins, such as Smac/DIABLO, and old proteins, such as heat shock proteins, playing new roles in regulating cell death.