A growing number of patients, particularly those with advanced, chronic coronary artery disease, experience symptoms of angina that are refractory to treatment with β-blockers, calcium-channel blockers, and long-acting nitrates, despite revascularization. The management of patients with refractory angina who are unsuitable for further revascularization is strikingly different across the world, and is contingent on local resources and available expertise. Mortality in this patient population has decreased, but enhancing quality of life remains a challenge. New treatment principles are emerging in current practice, such as metabolic modulation, therapeutic angiogenesis, and novel interventional techniques (coronary in-flow redistribution and approaches to chronic total occlusion). The contemporary management of refractory angina encourages individualized, patient-centred care in interdisciplinary, specialized clinics. Global initiatives are required to address complex clinical problem-solving for patients with refractory angina. In this Review, we discuss the epidemiology of refractory angina, and provide an update on the pharmacological, noninvasive, and interventional options that are available to these patients or are under development.