Interactions between microglia, the resident macrophages of the central nervous system (CNS), and myelin, the glial sheath on nerve fibers essential for rapid neural impulse transmission, are commonly studied in the context of neurotrauma and disease. However, interactions between microglia and myelin under normal physiological conditions have been largely overlooked. This review summarizes recent research indicating that the unique properties of microglia evident in disease states also enable microglia to regulate myelination during development and throughout life. This includes phagocytosis of cells and myelin membrane as well as the release of trophic factors, cytokines, and chemokines. The ability of microglia to sense neuronal activity and molecular features of the microenvironment enables them to optimize myelination by influencing early oligodendrogenesis, myelin formation, and removal of aberrantly targeted myelin. Understanding how microglia participate in myelination under normal conditions provides a new perspective that will increase understanding of developmental abnormalities.