microRNAs (miRNAs) are 21-23-nucleotide non-protein-coding RNA molecules that act as negative regulators of gene expression, modulating the stability and/or the translational efficiency of target messenger RNAs. This review describes miRNA regulation and function in tissue response to acute ischemia. We focused our attention on a subset of miRNAs that have been found de-regulated in different studies, suggesting that they may represent "master ischemic" miRNAs, playing a pathogenetic role in different components of tissue response to ischemia. First, we analyzed the role of miRNAs in cell response to hypoxia, a crucial component of ischemia, and in angiogenesis. Then, we describe miRNAs role in acute myocardial infarction as much as in hindlimb, cerebral, hepatic and retinal ischemia. The role played by specific miRNAs in the regulation of apoptosis, fibrosis, regeneration and myocardial arrhythmias is illustrated. The identification of specific miRNAs as key regulators of the response to ischemia has opened new clinical avenues. miRNAs may constitute excellent non-invasive disease biomarkers. Furthermore, innovative strategies targeting miRNAs, aimed to reduce the levels of pathogenic or aberrantly expressed miRNAs or to elevate the levels of miRNAs with beneficial functions, have been developed and could be applied in the treatment of ischemic diseases.