Recent studies have indicated that constitutive functions of microglia in the healthy adult central nervous system (CNS) involve immune surveillance, synapse maintenance and trophic support. These functions have been related to the ramified structure of 'resting' microglia and the prominent motility in their processes that provide extensive coverage of the entire extracellular milleu. In this review, we examine how external signals, and in particular, ionotropic neurotransmission, regulate features of microglial morphology and process motility. Current findings indicate that microglial physiology in the healthy CNS is constitutively and reciprocally regulated by endogenous ionotropic glutamatergic and GABAergic neurotransmission. These influences do not act directly on microglial cells but indirectly via the activity-dependent release of ATP, likely through a mechanism involving pannexin channels. Microglia in the 'resting' state are not only dynamically active, but also constantly engaged in ongoing communication with neuronal and macroglial components of the CNS in a functionally relevant way.