Both electrophysiologic and anatomical substrates are important in the generation and maintenance of atrial fibrillation. This review discusses the nature of re-entrant wavefronts in atrial fibrillation and the importance of anatomical structures, such as the pectinate muscles, in the generation and maintenance of re-entry. The involvement of the pectinate muscle structure on intra-atrial re-entry may have significant implications for both ablation and pharmacologic management of patients with atrial fibrillation.