Oncostatin M is a secreted cytokine involved in homeostasis and in diseases involving chronic inflammation. It is a member of the gp130 family of cytokines that have pleiotropic functions in differentiation, cell proliferation, and hematopoetic, immunologic, and inflammatory networks. However, Oncostatin M also has activities novel to mediators of this cytokine family and others and may have fundamental roles in mechanisms of inflammation in pathology. Studies have explored Oncostatin M functions in cancer, bone metabolism, liver regeneration, and conditions with chronic inflammation including rheumatoid arthritis, lung and skin inflammatory disease, atherosclerosis, and cardiovascular disease. This paper will review Oncostatin M biology in a historical fashion and focus on its unique activities, in vitro and in vivo, that differentiate it from other cytokines and inspire further study or consideration in therapeutic approaches.