Atrial fibrillation (AF) ablation is widely performed and is progressively supplanting drug therapy. Catheter-based AF ablation modalities have evolved progressively in parallel to our understanding of underlying mechanisms. Initial attempts to mimic the surgical maze procedure, which were based on the multiple wavelet model, failed because of adverse outcomes and insufficient effectiveness. A major advance was the targeting of pulmonary veins, which is highly effective for paroxysmal AF. Active research on the underlying mechanisms continues. The main challenge is reconnection, but procedures to minimize this are being developed. Ablation procedures for persistent AF are presently limited by suboptimal success rates and long-term disease progression that causes recurrences. Basic research into the underlying mechanisms has led to promising driver mechanism-directed clinical approaches along with pathways toward the prevention of atrial remodeling. Here, we review the role of basic research in the development of presently used AF-ablation procedures and look toward future contributions in improving outcomes.