Resolution of infections depends on the host's ability to mount a protective immune response. However, an exacerbated response to infections may result in deleterious lesions. Consequently, immunoregulatory mechanisms are needed to control immune response and prevent infection-associated lesions. Interleukin 10 may be a major regulator of innate and adaptive immunity in vitro and in animals, but its role in human infections is still unclear. Review of the published work reveals wide involvement of interleukin 10 in two major features of infectious diseases. On one hand, interleukin 10 prevents the development of immunopathological lesions that result from exacerbated protective immune response to acute and chronic infections. On the other hand, it is critically involved in persistence of bacteria and viruses by interfering with innate and adaptive protective immunity. Moreover, infections induce the expansion of interleukin-10-producing regulatory cells that are involved in protection against allergic diseases.