Nitroglycerin, first introduced over a hundred years ago, is now finding wider clinical applications. To a large degree, the renewed interest in the clinical pharmacologic usage of nitroglycerin is due to the availability of new formulations and drug delivery systems. The current review focuses on the physiological and pharmacological actions of nitroglycerin in mammals. Routes of nitroglycerin metabolism, biochemistry and absorption are discussed. The phenomenon of nitroglycerin tolerance is illustrated and related to specific quantitative alterations occurring at the cellular level. The cardiovascular effects of nitroglycerin are discussed in terms of its effects on coronary flow, the myocardium itself, and on the peripheral vasculature. The early speculation of Murrell (3) that nitroglycerin "would probably prove of service in the treatment of angina pectoris ... and other vascular disorders ..." has now been realized.