During atrial fibrillation (AF), multiple wandering propagation wavelets at high rates drift around both atria under controversial hierarchical models. Antiarrhythmic drugs modify the cardiac ionic currents supporting the fibrillation process within the atria, and can alter AF propagation dynamics and even terminate the arrhythmia. However, some other drugs, theoretically nonantiarrhythmic, may slightly block particular cardiac ionic currents through uncertain mechanisms in such a subtle way at regular heart rates that may have been pharmacologically overlooked. These potential effects might be better exposed at much higher activation rates as in AF, where atrial cells depolarize over 400 times per second. In this review, we aimed to compile and discuss results from several studies evaluating the net effect of profound sedation with propofol on atrial cells and atrioventricular (AV) conduction. Propofol is a very commonly used anesthetic agent, and its possible effect on AF dynamics has systematically not been taken into account in the myriad of clinical studies dealing with AF intracardiac recordings. The possible effect of sedation with propofol on AF was evaluated through the analysis of AF propagation patterns before and after its infusion in a series of patients submitted to pulmonary vein ablation. Effect on AV conduction will be discussed as well.