Interleukin-10 (IL-10) is a pleiotropic cytokine that modulates the function of several adaptive immunity-related cells. Although generally considered an immunosuppressive molecule, IL-10 possesses immunostimulatory properties in several in vitro and in vivo models. These very different outcomes are believed to depend upon experimental conditions, the dominant immune effector mediating a given immune response, the timing of IL-10 production/administration, and IL-10 dose and/or location of expression. In the present work, we review the current knowledge regarding IL-10 activity on adaptive immunity related cells, emphasize new insights on IL-10 molecular/cellular targets, and summarize the available data on the relationship between IL-10 and some pathological conditions (e.g. infectious diseases, autoimmunity, allergy, cancer and transplantation) involving adaptive immunity.