Interleukin-15 (IL15) is a cytokine that plays a major role in the development of inflammatory and protective immune responses to microbial invaders and parasites. It modulates immune cells of both innate and adaptive immune systems, and shares many biological activities with IL2. Unlike most soluble cytokines, IL15 is expressed in association with its high affinity IL15RA on the surface of IL15-producing cells, transmitting signals to target cells that express IL2RB and IL2RG receptor subunits. Binding to its receptor triggers JAK1 and JAK3 phosphorylation, as well as recruitment and subsequent phosphorylation of signal transducer and activator of transcription-3/STAT3 and STAT5. IL15 induces or enhances differentiation, maintenance, or activation of multiple T cell subsets including NK, NKT, Th17, Treg, and CD8+ memory cells. In monocytes, it stimulates production of IL8 and monocyte chemotactic protein 1/CCL2, which attract neutrophils and monocytes respectively to sites of infection. In mast cells, it rapidly induces tyrosine phosphorylation of STAT6 thereby regulating mast cell survival along with release of cytokines like IL4. IL15 exhibits anti-tumor activity independent of its effects on NK cells or CD8+ T cells. It also inhibits lipid deposition in adipocytes, and its circulating levels are decreased in obesity. Immunotherapy treatment utilizing recombinant IL15 offers an advantage over IL2 by not stimulating Treg cells, but has the drawback of associated toxicity at higher doses. Preclinical and early clinical studies have demonstrated potential for combining cancer vaccines with IL15 to enhance their anti-tumor response. Additionally it can be used for preconditioning CAR-T cells or engineering cells to express IL15 in vivo.