Cardiac allograft vasculopathy (CAV) is the most important cause of morbidity and mortality following cardiac transplantation. CAV is largely mediated by immunologic damage and infiltration of the endothelium, resulting in proliferation of vascular smooth muscle cells and subsequent luminal narrowing. There are various risk factors for the development and progression of CAV. Coronary angiography is the gold standard for the diagnosis of CAV; intravascular ultrasound also plays an important role. The management of CAV includes immunosuppression, drugs that modify conventional coronary artery disease risk factors, and percutaneous coronary intervention (PCI) or surgical revascularization for severe obstructive lesions. Although revascularization with PCI has a high immediate success rate, rates of in-stent restenosis are higher as compared with PCI of native coronary arteries, although the advent of drug-eluting stents has somewhat improved in-stent restenosis rates. Thus, the only definitive treatment of CAV is repeat transplantation. Randomized trials are needed to determine the optimal immunosuppressive and conventional risk factor-modifying agents and revascularization strategies for patients who develop CAV.