A type 1 cytokine-dependent pro-inflammatory response inducing classically activated macrophages is crucial for parasite control during protozoan infections but can also contribute to the development of immunopathological disease symptoms. Accumulating evidence indicates that interleukins 4, 13 and 10, transforming growth factor-beta, immune complexes and apoptotic cells elicited during these infections induce alternative activation states of macrophages, affecting disease outcome by, on the one hand, promoting parasite survival and proliferation and, on the other hand, limiting collateral tissue damage because of excessive type 1 inflammation. Thus, modulation of macrophage activation may be instrumental in allowing parasite persistence and long-term host survival.