Background The use of perioperative cardiac medical therapy among patients undergoing coronary artery bypass graft surgery (CABG) has not been closely examined. Objectives The objective of this study was to systematically review the medical literature examining the effects of perioperative cardiac medical therapy on clinical outcomes among patients undergoing CABG. Methods Using the Medline database and online clinical trial databases, we reviewed all randomized controlled trials (RCTs) and observational studies examining the effect of perioperative angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, antilipid agents (including statins), aspirin, β-blockers, and calcium-channel blockers on clinical outcomes. Results Our review identified 27 studies (6 RCTs, 21 observational studies), involving >700 000 patients, that examined the impact of perioperative medical therapy on clinical outcomes after CABG. Although studies provide conflicting results, the literature suggests that perioperative aspirin use may decrease inhospital mortality and myocardial infarction, whereas perioperative angiotensin-converting enzyme inhibitor use does not appear to be beneficial. Perioperative statin use reduces all-cause mortality at 30 days and cardiac death at 60 days and 1 year post-CABG but does not appear to reduce myocardial infarction or congestive heart failure rates. Multiple studies have demonstrated that pre- and postoperative β-blockers are associated with a decrease in atrial fibrillation. In addition, β-blockers may reduce inhospital and 30-day mortality, although these results are not consistent across all studies. Calcium-channel blockers do not appear to improve inhospital or 30-day mortality. No studies examined the perioperative use of angiotensin II receptor blockers or nonstatin antilipid agents among CABG patients. Conclusions The perioperative use of cardiac medical therapy among CABG patients remains understudied. Given their proven benefits among patients with cardiovascular disease and their potential to improve outcomes among CABG patients, further studies, particularly large RCTs, are needed.