Refractory angina refers to a group of patients with stable coronary atherosclerotic disease and angina symptoms, unresponsive to traditional medical management, while considered to be suboptimal candidates for revascularization procedures. Up to 15% of angina patients are considered to have refractory angina and, taking into account the aging population and the improvements in the treatment of stable coronary artery disease, the incidence of this entity is expected to increase. This review describes traditional and novel pharmacotherapies for symptoms relief and for long-term management of refractory angina. Mechanisms of action and relevant clinical trials are discussed and current recommendations from major European and US cardiovascular societies are reported.