Interleukin (IL)-10, initially described as cytokine synthesis inhibitory factor, is a pleotropic cytokine produced by many cell populations. Its main biological functions appear to be quite diverse: on the one hand it is involved in the limitation and termination of inflammatory responses and the regulation of differentiation and proliferation of several immune cells, and on the other hand it mediates immunostimulatory properties that support the elimination of infectious and non-infectious particles with limited inflammation. Numerous investigations, including expression analyses in patients, and both in vitro and in vivo studies suggest a major physiological and pathophysiological impact of IL-10. Activation of the neuro-endocrine axis following acute stress reactions leads to systemic IL-10 release, preventing hyperinflammatory reactions. IL-10 is overexpressed in many solid tumors and lymphomas and considered to promote further tumor development. In contrast, a relative IL-10 deficiency has been observed and is regarded to be of pathophysiological relevance in certain inflammatory disorders characterized by a type 1 cytokine pattern such as psoriasis. Recombinant human IL-10 has been tested in several clinical trials including rheumatoid arthritis, inflammatory bowel disease, psoriasis, organ transplantation, and hepatitis C. The results are heterogeneous and give new insight into the immunobiology of IL-10. However, further investigations would be desirable to better determine the effect/side effect profile as well as the best first line target indication and optimal therapeutic regimen.