Microglia play an important role in the development and maintenance of the central nervous system (CNS) under homeostatic conditions as well as during neurodegenerative diseases. Recent observations in human genomics and advances in genetic mouse models have provided insights into signaling pathways that control development, survival, proliferation and function of microglia. Alteration of these pathways contributes to the pathogenesis of CNS diseases. Here we review the current literature regarding the roles of these microglial pathways in both the normal and diseased brain and discuss areas that require further investigation.