Macrophages protect their host by engulfing foreign bodies within phagosomes that rapidly develop into microbicidal organelles. Numerous pathogens, such as species of Toxoplasma, Leishmania, Mycobacterium, Salmonella and Legionella, thrive in human macrophages, sometimes with disastrous effects. Defining the survival tactics of intracellular parasites is one approach to understanding macrophage function. Here, we briefly review phagosome maturation, then discuss how particular microbes may target particular host factors to short-circuit membrane traffic in macrophages. Recent studies support a new paradigm in which pathogens evade lysosomal degradation by entering macrophages within specialized lipid microdomains of the plasma membrane.