Cardiovascular disease (CVD) continues to be the leading cause of death and disability in the United States. Furthermore, over 40% of the US adult population is projected to have some form of CVD by 2030. Vascular smooth muscle cells (VSMCs) participate importantly in atherosclerosis, the major cause of myocardial infarction and stroke. MicroRNAs (miRNAs) are a class of small non-coding RNAs containing ~22 nucleotides. Studies using mouse models have shown that miRNAs are essential for cardiovascular development and function. Furthermore, miRNAs are required for proliferation and differentiation of VSMCs during embryonic development and for maintaining vascular contractile function, SMC contractile differentiation, and vascular remodeling in the postnatal stage. Numerous studies have linked altered miRNA expression to various diseases, indicating that miRNAs may play important roles in the pathogenesis of CVD.