Clinical trials in patients with pacemakers for sinus node dysfunction or atrioventricular block have highlighted the fact that desynchronization of ventricular contraction induced by right ventricular apical pacing is associated with long-term morbidity and mortality. These clinical data confirm pathophysiological results indicating that right ventricular apical pacing causes abnormal ventricular contraction, reduces pump function and leads to myocardial hypertrophy and ultrastructural abnormalities. In this manuscript, we discuss the clinical evidence for the adverse and beneficial effects of various right ventricular pacing sites, left ventricular pacing sites and biventricular pacing. We also propose a decisional algorithm for pacing modalities, based on atrioventricular conduction, left ventricular function and expected lifespan.