Current pacing practice is undergoing continuous and substantial changes. Initially pacing had an exclusively palliative role, since it was reserved for patients developing complete heart block or severe symptomatic bradycardia. With the appearance of novel pacing indications such as pacing for heart failure and atrial fibrillation, the effect of pacing site on cardiac function has become a critically important issue and a subject for consideration. It seems that the classical pacing site in the right ventricular apex is no longer the gold standard because of possible disadvantageous effects on cardiac function. The aim of this review article is to discuss the effect of right ventricular apical pacing on cardiac function including cellular and hemodynamic changes. We also aim to discuss the role of alternative pacing sites in the light of cardiac function.