MicroRNAs negatively regulate gene expression by promoting mRNA degradation and inhibiting mRNA translation. Recent studies have uncovered a cadre of muscle-specific microRNAs that regulate diverse aspects of muscle function, including myoblast proliferation, differentiation, contractility and stress responsiveness. These myogenic microRNAs, which are encoded by bicistronic transcripts or are nestled within introns of myosin genes, modulate muscle functions by fine-tuning gene expression patterns or acting as 'on-off' switches. Muscle-specific microRNAs also participate in numerous diseases, including cardiac hypertrophy, heart failure, cardiac arrhythmias, congenital heart disease and muscular dystrophy. The myriad roles of microRNAs in muscle biology pose interesting prospects for their therapeutic manipulation in muscle disease.