Killer lymphocytes are primary immune effectors of virus, certain bacteria, and tumor immunity and play a role in autoimmunity and transplant rejection. This article reviews progress in deciphering the mechanisms by which they kill target cells through induction of apoptosis by either the secretory, perforin/granzyme-based pathway or the nonsecretory pathway, (i.e., by triggering the cell-surface death receptor Fas (CD95) by the membrane-bound Fas ligand of the killer).