Studies on the gene structure, on the transcript, and on perforin protein are reviewed, including intracellular trafficking. Perforin transcription is tightly regulated and specific for CTL and NK. Two independent pathways for perforin induction exist, only one of them being IL-2 independent. Perforin expression in vitro and in vivo correlates with the functional expression of cytotoxicity in viral infection, transplant and tumor rejection, and in autoimmunity. Perforin together with granzymes is localized in cytolytic granules. However, the trafficking of those two proteins is quite different. Since the properties of perforin containing granules encompass the characteristics of secretory granules and of lyzosomes, the term granulosomes is used to describe this unique organelle. Evidence is reviewed to refute the concept that the homologous restriction factors of complement also restrict the lysis of homologous cells by perforin.