Background: Acute myocardial infarction (MI) remains a leading cause of death in the United States. There is evidence that primary (direct) percutaneous intervention (PCI) may improve survival and reduce morbidity in patients with acute MI. Methods: We present a concise, comprehensive, evidence-based literature review of modern techniques of primary PCI in patients with acute MI. A comparison to thrombolytic therapy, especially in selected patient subgroups is made. Rescue angioplasty is also addressed. Adjunctive pharmacology, economic implications, and feasibility of implementation are discussed. A brief discussion of experimental therapies is included. Results: Primary PCI is an acceptable alternative to thrombolytic therapy in patients with acute MI and may result in superior outcomes in select patient populations, especially the elderly, patients with prior coronary artery bypass surgery, those with congestive heart failure, and those in cardiogenic shock. Conclusions: Clinical trials support the use of primary PCI as first-line therapy for acute myocardial infarction. Patients in whom thrombolytic therapy is contraindicated or known to have reduced efficacy are also excellent candidates for this therapy. Ongoing advancements in equipment and adjunctive therapies continue to enhance delivery of this treatment as well as improve patient outcome.