Primary percutaneous coronary intervention (PCI) has emerged as the preferred therapy for acute ST-segment elevation myocardial infarction (STEMI), as multiple randomized clinical trials and pooled analyses have shown improved clinical outcomes compared with medical reperfusion. Unfortunately, medical centers with 24-hour PCI capability are concentrated in urban areas, relegating many patients in the United States to inferior medical reperfusion. Ongoing substantial research efforts are directed at optimizing mechanical reperfusion, including refinements in adjuvant medical therapy and the use of drug-eluting stents in the catheterization laboratory. Research efforts are also focusing on the implementation of streamlined transfer systems from community centers to tertiary care centers, akin to systems used in the trauma model. Furthermore, experience with the performance of primary PCI at community centers without onsite surgical backup is growing. This article summarizes data regarding the current state, challenges, and future directions of primary PCI for STEMI, emphasizing adherence to current American College of Cardiology/American Heart Association guidelines.