In the last decade, microRNAs (miRNAs) have revolutionized how we understand metabolism and disease. These small, 20- to 22-nucleotide RNA molecules fine-tune gene expression and can often coordinate multiple genes in a single pathway. Given the multifactorial nature of cardiovascular disease, it is perhaps not surprising that miRNAs have been shown to orchestrate many aspects of disease development, from modulating metabolic risk factors over a lifetime (eg, cholesterol and hormones) to controlling the response to an acute cardiovascular event (eg, inflammation and hypoxia). In this review, we discuss how miRNAs exert control over metabolic pathways that maintain vascular health and, when these pathways go awry, how miRNAs can be targeted for therapeutic modulation.