Macrophages are crucial in immunity to infection. They possess potent antimicrobial function, and efficiently process and present peptide antigens for T-cell activation. Despite this, the intracellular protozoan parasites Toxoplasma gondii, Trypanosoma cruzi and Leishmania spp. target macrophages for infection. Each has adopted unique strategies to subvert macrophage antimicrobial functions. The parasites sabotage killing activities through sophisticated manipulation of intracellular macrophage signaling pathways. These subversive activities are probably dictated by the need to evade microbicidal effector function, as well as to avoid proinflammatory pathology that can destabilize the host-parasite interaction. The molecular details of how intracellular protozoans manipulate macrophage signal transduction pathways for their own ends are beginning to emerge.