Atrial fibrillation (AF) is the most common cardiac arrhythmia disorder with significant associated morbidity and mortality. Several pathophysiological mechanisms have been proposed to explain the occurrence of AF. There is growing evidence that abnormalities of the cardiac autonomic nervous system (ANS), which includes the sympathetic, parasympathetic, and intrinsic neural networks, are involved in the pathogenesis of AF. This review will examine the anatomical and pathophysiological concepts of the cardiac neural network, the relationship between the ANS and the pathophysiology of AF, and the potential benefits and limitations of neuromodulation in the treatment of this arrhythmia. We conclude that activation and remodeling of the cardiac ANS are involved in the initiation and maintenance of AF, and the sympathetic/parasympathetic balance plays an important role in the substrate of AF. In addition, modulation of cardiac ANS function through ganglion plexus ablation may allow control of AF. Although the role of the ANS has long been recognized, a better understanding of the complex interactions of its various components will lead to improved treatment of AF.