Modern management of acute myocardial infarction is built on a clinical evidence base drawn from many studies undertaken over the past three decades. The evolution in clinical practice has substantially reduced mortality and morbidity associated with the condition. Key to this success is the effective integration of antithrombotic therapy combined with timely reperfusion, either primary percutaneous coronary intervention or fibrinolysis for ST-elevation myocardial infarction, and invasive investigation and revascularisation for non-ST-elevation myocardial infarction, underpinned by risk stratification and optimised systems of care. After the development of troponin assays for the detection of myonecrosis, the universal definition and classification of myocardial infarction now indicates the underlying pathophysiology. Additionally, an increasing appreciation of the importance of adverse events, such as bleeding, has emerged. Remaining challenges include the effective translation of this evidence to all patients with myocardial infarction, especially to those not well represented in clinical trials who remain at increased risk of adverse events, such as elderly patients and those with renal failure. On a global level, the epidemic of diabetes and obesity in the developed world and the transition from infectious diseases to cardiovascular disease in the developing world will place an increasing demand on health-care infrastructures required to deliver time-dependent and resource-intensive care. This Seminar discusses the underlying pathophysiology, evolving perspectives on diagnosis, risk stratification, and the invasive and pharmacological management of myocardial infarction.