Depending on the cytokine environment, macrophages can differentiate into distinct subsets that perform specific immunological roles. In this regard, the functions of macrophages activated by interferon γ, referred to as classically activated macrophages, have been extensively documented, particularly during immune responses to infection. Recently, it was recognized that macrophages exposed to cytokines generated by T helper cell type 2 (Th2) cells exert an alternative activation program. However, the nature and functions of alternatively activated macrophages are ill defined. Evidence for the presence of alternatively activated macrophages and their possible influence in the outcome of several parasite diseases are discussed here.