microRNAs (miRs) are short, approximately 22-nucleotide-long non-coding RNAs involved in the control of gene expression. They guide ribonucleoprotein complexes that effect translational repression or messenger RNA degradation to targeted messenger RNAs. miRs were initially thought to be peculiar to the developmental regulation of the nematode worm, in which they were first described in 1993. Since then, hundreds of different miRs have been reported in diverse organisms, and many have been implicated in the regulation of physiological processes of adult animals. Of importance, misexpression of miRs has been uncovered as a pathogenic mechanism in several diseases. Here, we first outline the biogenesis and mechanism of action of miRs, and then discuss their relevance to heart biology, pathology, and medicine.