This review focuses on the biological effects of the newly discovered cytokine, interleukin 15 (IL-15), in chronic inflammatory disorders. IL-15 shares biological activities with IL-2, and like IL-2 it is a member of the four-helix bundle cytokine family. IL-15 interacts with a heterotrimeric receptor that consists of the β and γ subunits of the IL-2 receptor (IL-2R) as well as a specific, high-affinity IL-15-binding subunit, IL-15Rα. IL-15 is produced by macrophages and various other cells in response to environmental stimuli and infectious agents, and it is important for the growth and differentiation of T and B lymphocytes, natural killer cells, macrophages, and monocytes as well as it activates a number of important intracellular signaling molecules, including the Janus kinases and members of the transcription factor family of signal transducers and activators of transcription. These facts suggest that IL-15 may play a pivotal role both in protective immune responses and in the pathogenesis of various chronic immuno-inflammatory disorders. The important new insight into the role of IL-15 in diseases such as rheumatoid arthritis, sarcoidosis, chronic hepatitis C, and ulcerative colitis are reviewed in this paper.