Macrophages are terminally differentiated cells of the mononuclear phagocytic system, which play an indispensable role in the maintenance of homeostasis and defense. Macrophages can be phenotypically polarized by the microenvironment to mount specific functional responses. Polarized macrophages can be broadly classified into two main groups: classically activated macrophages (M1), whose prototypical activating stimuli are IFN-γ and LPS, and alternatively activated macrophages (M2), further subdivided in M2a (after exposure to IL-4 or IL-13), M2b (immune complexes in combination with IL-1β or LPS) and M2c (IL-10, TGF-β or glucocorticoids). M1 exhibit potent microbicidal properties and promote strong IL-12-mediated Th1 responses, while M2 macrophages support Th2- associated effector functions. Here we review the main functions of polarized macrophages in Chagas disease and discuss their potential value in evaluating disease severity.