Atrial fibrillation (AF) is highly prevalent and accounts for significant morbidity, mortality, and health care costs. Catheter ablation has become a therapeutic option in the management of this challenging arrhythmia. To optimize procedure safety and long-term efficacy, innovative technologies and ablation strategies have been targeting either the triggers initiating AF or the substrate responsible for its maintenance. Pulmonary vein (PV) isolation, initially limited to the PVs, has been modified to encompass the left atrial myocardium surrounding the PV ostia, namely the LA-PV antra. Our current intracardiac echo-guided approach to PV antra isolation, including the adjunct of superior vena cava isolation, has likely accounted for higher success rates by electrically isolating further AF trigger sites, modifying the substrate for AF maintenance and possibly by modulating a dysfunctional autonomic cardiac nervous system. However, the long-term outcome following ablation of permanent AF can be further improved by incorporating adjunctive ablation strategies to PV isolation, such as targeting ablation at sites exhibiting complex atrial fractionated electrograms (CFAEs)during AF or at sites exhibiting the so-called AF nests during real-time spectral mapping in sinus rhythm.