Cardiovascular disease is a major challenge to nephrologists, whether we deal with patients with pre-end-stage renal failure, on dialysis or after successful renal transplantation. It is the most common cause for death in patients with a functional allograft, and prevents many dialysis patients from being engrafted. Coronary artery disease is a diagnostic and therapeutic challenge, as it differs in some respects from that seen in nonuremic cohorts, and lacks much of the evidence-base on which therapeutic intervention rests. This review examines the experimental and clinical literature on cardiovascular disease in uremia, focusing on coronary artery disease. We focus on the incidence, presenting syndromes, screening tools, and interventions in the context of acute and chronic coronary syndromes. Recent evidence comparing coronary angioplasty, coronary artery stenting, and bypass surgery in subjects with renal failure is also reviewed. Coronary artery disease is more prevalent in uremia, more difficult to diagnose and less rewarding to treat compared to non-uremic subjects. Many more randomized trials are needed. In the absence of information from such trials, we advocate aggressive control of conventional and novel cardiovascular risk factors, and early intervention for symptomatic coronary disease.