Secretory lysosomes are specialized organelles that combine catabolic functions of conventional lysosomes with an inducible secretory potential. They are present in various hematopoietic cell types commonly characterized by the need for rapid mobilization and secretion of effector proteins. As an example, the cytotoxic effector function of T cells and natural killer cells strictly depends on the activation-dependent mobilization of such vesicles to the cytotoxic immunological synapse. This review focuses on some molecules that have been identified as cargo of secretory lysosomes and which play a major role in effector function of CTL and NK cells. We also briefly point to the fact that the dysregulation of formation and transport of secretory vesicles is causative for severe immunodeficiencies and autoimmunity observed in patients and also in mice that have been used as representative model systems to analyze the pathophysiological relevance of secretory vesicles in vivo.