The type of immune response a host can raise against an invading parasite may often be decisive between chronicity or clearance, and in the worst cases between host survival and death. Helper T cells are key to determining whether antibody-mediated, inflammatory or cytolytic responses will be predominant. Interleukin 10 (IL10) is widely recognized to be the most important cytokine for anti-inflammatory reactions and tends to be associated to chronicity in quite a few types of viral infections. On the other hand, it has also been associated to tissue preservation in chronic viral disease. This review summarizes the most recent data available in the literature on this pivotal cytokine during experimental viral infection and in the clinical setting.