MicroRNAs are short noncoding RNAs that post-transcriptionally regulate gene expression. Their function is to fine-tune protein levels, thereby reducing gene expression noise. MicroRNAs serve critical functions during brain development, sculpting the transcript landscapes that direct cell proliferation, migration, and differentiation. In the mature brain, microRNAs impose stability on gene expression patterns to protect the constancy of network behavior while also facilitating the mechanics of synaptic plasticity. Brain diseases feature alterations in levels of specific microRNAs which influence injury and repair processes including changes to neuronal and glia morphology, immune and inflammatory responses, and cellular metabolism. MicroRNAs are also found within the extracellular space, including circulating in the cerebrospinal fluid and plasma. Characterization of biofluid microRNAs indicates some have CNS origins leading to the idea that microRNAs function in local and long-distance signalling. This chapter reviews the microRNA pathway and functions in the brain, the physical forms of extracellular microRNAs including encapsulation within extracellular vesicles, the changes to circulating microRNAs in brain diseases and evidence that circulating microRNAs come from the brain, and the effects, if any, of extracellular microRNA on recipient cells. The chapter also reviews the clinical applications of these findings, including diagnostic point-of-care testing and as therapeutic targets.