As the US population ages, the pool of patients with coronary artery disease and stable angina is projected to grow. Conventional approaches with mechanical and pharmacological therapies have made inroads toward curbing this trend, reducing the risk of future myocardial infarction and cardiac death. However, the potential benefits of currently available antianginal medications are limited by reduced work capacity, orthostasis, and important drug-drug interactions. A new approach is represented by the piperazine derivatives trimetazidine (TMZ) and ranolazine (RNZ). TMZ acts to partially inhibit fatty acid oxidation, thus shifting myocardial energy metabolism to a lower oxygen-consuming state. A total of 16 randomized trials have been completed with TMZ. In the US market, 6 trials have been completed with RNZ. RNZ has been separately classified as a late sodium channel inhibitor, which reverses action potential prolongation, suppresses early after-depolarizations, and terminates resultant ventricular tachycardia. Though it has some of the same fatty acid oxidation properties as TMZ, this is not considered its primary mechanism of action. This paper reviews medical approaches to chronic stable angina and highlights RNZ as an important advance for patients and clinicians in the US market.