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An explosion of findings driven by powerful new technologies has expanded our understanding of microglia, the resident immune cells of the central nervous system (CNS). This wave of discoveries has fueled a growing interest in the roles that these cells play in the development of the CNS and in the neuropathology of a diverse array of disorders. In this review, we discuss the crucial roles that microglia play in shaping the brain-from their influence on neurons and glia within the developing CNS to their roles in synaptic maturation and brain wiring-as well as some of the obstacles to overcome when assessing their contributions to normal brain development. Furthermore, we examine how normal developmental functions of microglia are perturbed or remerge in neurodevelopmental and neurodegenerative disease.