The role of microglia within the central nervous system (CNS), and their contribution to processes critical for both normal function and the development of pathology have expanded significantly in recent years. Distinct microglial subpopulations are described that exert differential effects depending on region, environmental cues and activation state. This has led to the proposition of microglia as a novel therapeutic target in a variety of CNS disorders. Exercise has recently been shown to reduce the chronic activation and aberrant regulation of microglia that occurs during pathology, and to promote the adoption of neuroprotective phenotypes. This is thought to translate into decreased destruction of dopaminergic neurons in models of Parkinson's disease, the promotion of hippocampal neurogenesis, and the reduction of age-induced neuroinflammation and microglial priming. The present review will detail the emerging evidence suggesting microglial modulation as a key mechanism through which exercise exerts beneficial effects on the CNS. Here, we will present the role of microglia within select CNS processes/disorders, and describe how physical exercise improves CNS well-being by directly acting through microglia. Finally, we discuss considerations of implementation of exercise as a therapeutic intervention in neurological disorders.