MicroRNAs (miRNAs) are a class of regulatory small RNAs that have fundamentally transformed our understanding of how gene networks are regulated representing one of the most exciting areas of the modern cardiology research. Among all known miRNAs, miR-208a is one of the most important heart-enriched miRNA playing a crucial role in the heart health and disease. miR-208a is a member of a miRNA family that also included miR-208b and is encoded by an intronic region of the Myh6 gene. Within the heart, miR-208a and miR-208b are involved in the regulation of the myosin heavy chain isoformswitch during development and in pathophysiological conditions. miR-208a is sufficient to induce arrhythmias, cardiac remodeling, and to regulate the expression of hypertrophy pathway components and the cardiac conduction system. Recently, the identification of miR-208a in the bloodstream has led to a great clinical interest to use this molecule as a potential noninvasive biomarker of myocardial injuries.