Microglia are the resident immune cells of the central nervous system (CNS), which have been classically viewed as involved in CNS responses to damage and tissue repair. However, microglia are constantly sensing neuronal network activity and changes in the CNS milieu, establishing complex state-dependent microglia-neuron interactions that impact their functions. By doing so, microglia perform a wide range of physiological roles, including brain homeostasis maintenance, control of neural connectivity, network function modulation, as well as functional and morphological plasticity regulation in health and disease. Here, the author reviews recent evidence of the modulations induced by microglia, a highly heterogeneous cell type, on synaptic and intrinsic neuronal properties, and on neuronal network patterns during perinatal development and adulthood. The reviewed evidence clearly indicates that microglia are important, if not essential, for brain function and plasticity in both health and disease.