Humans live in harmony with much of the microbial world, thanks to a sophisticated immune system. As the first line of defense, macrophages engulf, digest, and display foreign material, then recruit specialists to eliminate potential threats. Yet infiltrators exist: certain fungi, viruses, parasites, and bacteria thrive within sentinel macrophages. By scrutinizing the life styles of these shrewd microbes, we can deduce how macrophages routinely mount an effective immune response. The bimorphic life cycles of three pathogens have dramatic consequences for phagosome traffic. In the transmissible state, Leishmania spp., Coxiella burnetii, and Legionella pneumophila block phagosome maturation; after a pregnant pause, replicative forms emerge and thrive in lysosomes.