The immune system has evolved a variety of strategies to protect the host from detrimental effects of pathogens and tumour cells; the most beneficial outcome, however, is induction of an apoptotic death for the offending cell. Immune-mediated killing occurs through granule secretion and ‘death receptor’ pathways. Cytotoxicity assays have traditionally evaluated membrane permeabilization. With the realization that death in vivo is apoptotic, a host of novel approaches have been devised to evaluate this form of physiological cell death.