The current era has witnessed dramatic improvement in the treatment of acute myocardial infarction, due in large part to the more widespread use of thrombolytic therapy aimed at quickly restoring perfusion in the infarct-related artery. This review addresses the role of adjunctive pharmacologic therapy in the thrombolytic era, recognizing that much of the available clinical trial data supporting the role of adjunctive pharmacologic treatment strategies was conducted in patient populations not widely exposed to reperfusion therapy. This review, therefore, explores the data supporting the incremental benefit of therapy with beta blockers, nitrates, angiotensin-converting enzyme inhibitors, or magnesium in addition to thrombolytic therapy. Heparin and aspirin will not be discussed.