Transplant coronary artery disease (TCAD) remains the most significant cause of morbidity and mortality after orthotopic heart transplantation. Transplant coronary artery disease is largely an immunologic phenomenon, driven by an inflammatory milieu consisting of multiple cell types that contribute to fibromuscular and smooth muscle cell proliferation with subsequent coronary obstruction. Multiple clinical factors contribute to the development of TCAD. Coronary angiography is the gold standard for the diagnosis of TCAD. Current treatments for TCAD include pharmacotherapy, percutaneous coronary intervention, and repeat transplantation, although other novel therapies are emerging. Although percutaneous coronary intervention has generally demonstrated high procedural success rates, it has been plagued by a high incidence of in-stent restenosis. Drug-eluting stents reduce in-stent restenosis compared with bare metal stents. Repeat transplantation is the only definitive treatment. Prospective randomized trials comparing different pharmacotherapies as well as revascularization strategies are needed to identify the optimal therapy for patients who develop TCAD.