Achieving early reperfusion with thrombolytic agents or primary percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) is the cornerstone of current therapy. Two advances in pharmacologic therapy are: (1) bolus thrombolysis, which simplifies therapy, reduces door-to-needle time, and reduces the potential for medication errors, and (2) Low-dose fibrinolytic therapy combined with a glycoprotein (GP) IIb/IIIa inhibitor which can achieve higher rates of reperfusion than fibrinolytic therapy alone. In addition, the IIb/IIIa inhibitor as part of the reperfusion regimen will support any acute-phase interventions that are performed. The combination of fibrinolytic therapy and GP IIb/IIIa inhibition to "facilitate" PCI is being examined in TIMI-14, SPEED, and GUSTO IV. Early findings in the SPEED trial have shown promising results with "facilitated" PCI when patency is achieved before PCI is attempted. Results of these trials will further define the role of combination therapy in facilitating mechanical interventions.