Recent years have seen significant changes in the way scientists view microglia and their role in health and disease. For decades, it was presumed that microglia were stationary, inactive immune cells in the brain, waiting for an immunologic insult to call them into action. In contrast, modern imaging techniques have revealed that microglia are constantly in motion, surveying their environment. Lineage tracing studies have led to the understanding that microglia are part of a larger family of cells, called tissue-resident macrophages, which arise from early yolk sac progenitors during embryogenesis and engraft nearly every organ in the body. Microglia, and all tissue-resident macrophages, rely on signaling through CD115 (the colony stimulating factor 1 receptor) for survival, primarily through the ligand, macrophage colony-stimulating factor. However, it is now understood that some microglia have a specific need for another CD115 ligand, Interleukin-34, which is only shared with Langerhans cells in the skin. In contrast to classical views, recent evidence suggests that the primary functions of microglia may occur during postnatal neurodevelopment and adult homeostasis, as absence or impairment of microglia results in a pathology separate from inflammatory immune function. In summary, these advances suggest that microglia might eventually be utilized or targeted to improve disease outcomes via encouraging or enhancing their health-promoting homeostatic functions.