The invasive management of atrial fibrillation (AF) has been considerably changed by the identification of major sites of AF initiation and/or maintenance within the pulmonary vein antra. Percutaneous catheter ablation of these targets has become the standard of care for sustained maintenance of sinus rhythm. Long-term failure of ablation is related to an inability to create a durable transmural lesion or to identify all of the non-pulmonary vein arrhythmia triggers. Pharmacological challenges during catheter ablation have been suggested to improve outcomes in both paroxysmal and persistent AF. Herein we review the mechanism and evidence for the use of pharmacological adjuncts during the catheter ablation of AF.