Oligodendrocyte precursor cells (OPCs) play diverse roles in the brain, extending beyond their classically recognized contributions to oligodendrogenesis and myelination.In the developing and adult visual system, OPCs have been shown to remodel axons and to eliminate synapses through phagocytic engulfment.The engulfment of synapses by OPCs is influenced by multiple factors, including neural activity and molecular signals from other brain cells.Future work is needed to define the biological consequences and underlying molecular mechanisms of synapse engulfment by OPCs. Oligodendrocyte precursor cells (OPCs) are non-neuronal brain cells that give rise to oligodendrocytes, glia that myelinate the axons of neurons in the brain. Classically known for their contributions to myelination via oligodendrogenesis, OPCs are increasingly appreciated to play diverse roles in the nervous system, ranging from blood vessel formation to antigen presentation. Here, we review emerging literature suggesting that OPCs may be essential for the establishment and remodeling of neural circuits in the developing and adult brain via mechanisms that are distinct from the production of oligodendrocytes. We discuss the specialized features of OPCs that position these cells to integrate activity-dependent and molecular cues to shape brain wiring. Finally, we place OPCs within the context of a growing field focused on understanding the importance of communication between neurons and glia in the contexts of both health and disease.