Cytotoxic lymphocytes mediate immunity against viruses and surveillance against neoplastic transformation. They kill target cells by multiple mechanisms, but utilize a pore-forming protein, perforin, and a family of serine proteinases as their principal means of inflicting cell death. Recent studies have demonstrated that perforin and serine proteinases synergistically trigger an endogenous pathway of apoptosis resulting in dissolution of the target cell nuclear membrane and DNA fragmentation. These changes may be secondary to inappropriate activation of p34cdc2 kinase and the subsequent derangement of cell cycle control. As discussed by Mark Smyth and Joseph Trapani, the immediate molecular targets of perforin/granzyme-mediated apoptosis are still unclear, though candidate molecules with homology to cell death gene products from primitive organisms are currently under close scrutiny.