Multivessel coronary artery disease is characterized by involvement of greater than 1 epicardial coronary artery or the unprotected left main. The choice of revascularization strategy in this setting remains a critical issue in cardiology. Although coronary artery bypass grafting has traditionally been the revascularization strategy for most patients with multivessel disease, there has been a gradual shift toward percutaneous revascularization. Early randomized clinical trials showed coronary artery bypass grafting to be superior to medical therapy. However, trials comparing coronary artery bypass grafting to bare metal stenting have not shown a mortality benefit. Advancements in interventional techniques will continue to challenge the notion that coronary artery bypass grafting is the standard therapy for patients with multivessel coronary disease. Several ongoing randomized clinical trials comparing coronary artery bypass grafting to drug-eluting stents will provide valuable insight into the role of each procedure. In this article, we review the existing literature and discuss future directions in the management of the patient with multivessel disease.