Despite many years of research, the mechanisms of atrial fibrillation (AF) are still poorly understood, and we currently are unable to adequately treat most patients with AF. Recently, the demonstration in both human and animal studies that the pulmonary veins (PVs) and the posterior left atrial (LA) wall play a substantial role in triggering and in driving the fibrillatory activity has opened new avenues for research into the mechanisms of initiation and maintenance AF at many levels of integration. This article focuses on recent studies at the whole-heart level that support the hypothesis that maintenance of AF, whether paroxysmal or persistent, may depend on the periodic activity of a small number of rotors in the posterior LA wall-PV region. These rotors activate the atria at exceedingly high frequencies and result in fibrillatory conduction. Recent clinical studies involving either segmental PV isolation or circumferential PV ablation support this view. Such encouraging results suggest that collaboration between basic and clinical electrophysiologists will lead to a more precise understanding of the manner in which rotors stabilize in the PV-LA junction, which should open new doors for the development of innovative approaches for the prevention, diagnosis, and treatment of AF.