Intracellular pathogens are a major cause of global morbidity and mortality. While this alone establishes their medical importance, they are also a focus of special interest because of their unique lifestyles. Many of these organisms have evolved to reside within the hostile environment of macrophages. Given that these innate immune effector cells are normally programmed to destroy ingested prey and promote the development of adaptive immunity, this is one of the ultimate paradoxes in the study of host–pathogen interactions. The success of these microbes is dependent on diverse strategies including the disruption of macrophage cell regulation, the ability to nullify macrophage microbicidal effector mechanisms, and other special adaptations to an intracellular lifestyle. Here, we review a series of well established survival paradigms that have emerged that illustrate this behaviour.