Current therapeutic approaches to restore blood flow in stenotic blood vessels involve the use of percutaneous devices and coronary bypass surgery. In all procedures that disrupt the normal integrity of the blood vessels, there is an increased incidence of vessel luminal narrowing, termed restenosis. Restenosis, arbitrarily defined as greater than 50% narrowing of vessel diameter compared with the reference vessel, is modulated by genetic background and diseases that affect the cardiovascular system, including diabetes, hypertension, and hypercholesterolemia. In the 1970s, Andreas Gruntzig pioneered the use of transluminal dilatation of coronary arteries for symptomatic coronary artery disease and reported a 19% rate of restenosis (6 of 32 patients). 1–3 Subsequent studies demonstrated a restenosis rate of approximately 33%. 4 More than 25 years later, despite pharmacological and mechanical approaches to reduce the incidence of restenosis, it remains a significant problem, especially in high-risk patient groups, limiting overall success. Restenosis after percutaneous intervention is characterized by platelet aggregation, release of growth factors, inflammatory cell infiltration, medial smooth muscle cell proliferation and migration, and extracellular matrix remodeling. The vascular response to injury depends not only on the cells within the vessels but is also modulated by circulating bone marrow–derived cells. Understanding the molecular mechanisms underlying the physiological healing response and the pathological restenosis response has been the focus of extensive investigations, which have led to the development of novel approaches to control the pathological formation of the neointima. In this review, we will focus on some of the molecular mechanisms responsible for the abnormal neointimal hyperplasia, specifically focusing on cell cycle and microRNA (miRNA) in the vascular smooth muscle.