Cardiac transplantation has emerged as a valuable therapy for various end-stage cardiac disorders. Cardiac allograft vasculopathy (CAV), an unusually accelerated and diffuse form of obliterative coronary arteriosclerosis, determines long-term function of the transplanted heart. Cardiac allograft vasculopathy is a complicated interplay between immunologic and nonimmunologic factors resulting in repetitive vascular injury and a localized sustained inflammatory response. Dyslipidemia, oxidant stress, immunosuppressive drugs, and viral infection appear to be important contributors to disease development. Endothelial dysfunction is an early feature of CAV and progresses over time after transplantation. Early identification of CAV is essential if long-term prognosis is to be improved. Annual coronary angiography is performed for diagnostic and surveillance purposes. Intravascular ultrasound is a more sensitive diagnostic tool for early disease stages and has revealed that progressive luminal narrowing in CAV is in part due to negative vascular remodeling. Because of the diffuse nature of CAV, percutaneous and surgical revascularization procedures have a limited role. Prevention of CAV progression is a primary therapeutic goal.