Ischemic stroke remains a leading cause of death and disability with few treatment options. MicroRNAs (miRs) are short, non-coding RNAs that regulate gene expression. They have important potential applications as biomarkers for stroke severity and outcome, as well as presenting unique possibilities for interventions to minimize injury and improve recovery and outcome following stroke. MiRs function by binding messenger RNAs (mRNA) and silencing translation of target genes. Endogenous miR expression levels change in response to stress, and they can be altered by application of exogenous nucleotides - miR mimics - to increase or inhibitors to decrease levels of specific miRs. By virtue of their relatively short binding sequences, a single miR can simultaneously modulate numerous related gene targets. As miR expression can be cell-type specific, miRs can also be used to target specific brain cell types, such as microglia and astrocytes, which helps determine neuronal cell fate following stress. MiR-based therapeutics may therefore provide a novel approach to the development of effective therapeutics for ischemic stroke.