The identification of non-coding RNA species, previously thought of as 'junk' DNA, adds a new dimension of complexity to the regulation of DNA, RNA and protein. MicroRNAs are short non-coding RNA species that control gene expression, are dysregulated in settings of cardiac and skeletal muscle disease and have emerged as promising therapeutic targets. MicroRNAs specifically enriched in cardiac and skeletal muscle are called myomiRs and play an important role in cardiac pathology and skeletal muscle biology. Moreover, microRNA profiles are altered in response to exercise and disease; thus, their potential as therapeutic drug targets is being widely explored. In the cardiovascular field, therapeutic inhibition of microRNAs has been shown to be effective in improving cardiac outcome in preclinical cardiac disease models. MicroRNAs that promote skeletal muscle regeneration are attractive therapeutic targets in muscle wasting conditions where regenerative capacity is compromised.