The purpose of this paper is to review the randomized controlled trial (RCT) data investigating cardiac medical therapy for patients after coronary artery bypass grafting (CABG). We identified RCTs with > or =100 enrolled patients that examined the impact of cardiac medical therapy on outcomes > or =1 year after CABG. The MEDLINE database was searched for trials conducted between 1966 and 2004 on the following medications: aspirin, antilipid agents, beta-blockers, calcium channel blockers (CCBs), nitrates, and angiotensin-converting enzyme (ACE) inhibitors. Both aspirin and antilipid agents were found to reduce the progression of atherosclerosis and the occurrence of graft occlusion. Cardiovascular events were decreased with antilipid agents. In small trials, beta-blockers and CCBs failed to decrease the incidence of cardiovascular events. No RCTs examined nitrates, and one small RCT documented a reduction in cardiovascular events among patients treated with ACE inhibitors. We conclude that few RCTs have examined the efficacy of cardiac medical therapy in post-CABG patients. Based on current RCT evidence, aspirin and antilipid agents should be used routinely after CABG. However, current data do not support the use of beta-blockers, CCBs, and nitrates, and more evidence is needed regarding the use of ACE inhibitors.