Interleukin-15 (IL-15) is a 14-15 kDa polypeptide that belongs to the four alpha-helix bundle family of cytokines and was originally discovered due to its T cell proliferative activity. It utilizes the signal transducing b/g polypeptides of the IL-2 receptor complex thus sharing many biological activities with IL-2, in addition to its high affinity private receptor subunit IL-15Ra. Accumulating evidence indicates that the biological relevance of IL-15 may not solely be confined to T lymphocytes, but to a variety of cell populations within the immune system as well as outside the immune system of the host. The expression of both IL-15 and its high affinity receptor component, IL-15Ra are readily demonstrable in a wide variety of tissues and appear to be augmented in response to environmental/stress stimuli and infectious agents. There is increasing evidence to suggest that IL-15 may play an important role in protective immune responses, allograft rejection and the pathogenesis of autoimmune diseases where mononuclear cell infiltration is a hallmark feature. Herein, the effects of IL-15 on cells associated with host defense, immunity and inflammation are reviewed and support a central role for this cytokine in orchestrating multiple aspects of effector functions in immunity and inflammation.