Right ventricular septal pacing has been long touted as a more physiologic alternative to right ventricular apical pacing. This article reviews the physiologic and clinical evidence for right ventricular septal versus apical pacing, and presents a novel angiographic technique for efficient attainment of the optimal septal pacing site. The reasons for equivocal clinical findings in septal versus apical pacing studies are discussed, and a new strategy for non-apical pacing clinical trial design utilizing comparative anatomic assessment of septal pacing site versus clinical outcome is proposed.