Patients with refractory angina are not candidates for revascularization and have both class III or IV angina and objective evidence of ischemia despite optimal medical therapy. An estimated 300,000 to 900,000 patients in the United States have refractory angina, and 25,000 to 75,000 new cases are diagnosed each year. This review focuses on treatment strategies for refractory angina and includes the mechanism of action and clinical trial data for each strategy. The pharmacological agents that have been used are ranolazine, ivabradine, nicorandil, L-arginine, testosterone, and estrogen; currently, only L-arginine, testosterone, and estrogen are approved by the Food and Drug Administration. Results with the noninvasive treatments of enhanced external counterpulsation and transcutaneous electrical nerve stimulation are provided. Invasive treatment strategies including spinal cord stimulation, transmyocardial revascularization, percutaneous myocardial revascularization, and gene therapy are also reviewed.