The case for a rate-lowering approach to the prophylaxis of ischemia, the underlying cause of angina, was always firmly grounded in physiology and therapeutics. What it lacked, until the research effort sparked in 1979 by the discovery of the If current, the central sinoatrial determinant of heart rate, was pharmacological embodiment. Ivabradine, approved in 2005 for angina prevention, displays the efficacy and safety profile of a specific and selective If inhibitor that was predicted on pharmacological first principles: noninferiority versus atenolol and amlodipine in times to ST-segment depression and limiting angina, with none of the extraneous and negative hemodynamic, inotropic or metabolic effects associated with -blockade or calcium channel blockade. First principles also predict improved survival, which awaits confirmation in a clinical trial...