The Fourth Universal Definition of Myocardial Infarction recommends a classification based on aetiology, in recognition that the underlying pathophysiology of myocardial infarction influences the approach to investigation and treatment. Type 1 myocardial infarction occurs due to atherosclerotic plaque rupture with thrombosis, whereas type 2 myocardial infarction occurs due to an imbalance in myocardial oxygen supply or unmet need in myocardial oxygen demand, without atherothrombosis, usually in the context of another acute illness. In this state-of-the-art review, the diagnosis, investigation, and treatment of patients with type 2 myocardial infarction are considered, with general advice for clinical practice and a consideration of future research directions.