The identification of pulmonary veins as a trigger for atrial fibrillation (AF) has led to pulmonary vein isolation (PVI) as a key ablation target. However, PVI alone does not prevent recurrent AF in many patients, and additional ablation strategies have not improved outcomes. This review highlights emerging approaches that target atrial cardiomyopathy (ACM), the underlying anatomic, electrical, and/or autonomic disease affecting the atria. These approaches include risk factor modification, targeting epicardial adipose tissue (EAT), tissue fibrosis, oxidative stress, and the inflammasome, as well as early anti-AF therapy. Risk factor modification, such as weight loss and blood pressure control, is crucial. EAT, which is unique for its proximity to the heart and unique transcriptome and secretome, can contribute to AF through various mechanisms and is a modifiable therapeutic target. Atrial fibrosis, a central feature of ACM, can be targeted with drugs like angiotensin-converting enzyme inhibitors and beta-blockers. Oxidative stress, mediated by reactive oxygen species (ROS), can be addressed with antioxidants and NOX inhibitors. The inflammasome, particularly NLRP3, plays a role in AF pathogenesis, and selective inhibitors are being explored. Early intervention to prevent AF progression, such as antiarrhythmic drug therapy, may also be beneficial. These non-ablation approaches offer potential adjunctive therapies to improve AF outcomes.The identification of pulmonary veins as a trigger for atrial fibrillation (AF) has led to pulmonary vein isolation (PVI) as a key ablation target. However, PVI alone does not prevent recurrent AF in many patients, and additional ablation strategies have not improved outcomes. This review highlights emerging approaches that target atrial cardiomyopathy (ACM), the underlying anatomic, electrical, and/or autonomic disease affecting the atria. These approaches include risk factor modification, targeting epicardial adipose tissue (EAT), tissue fibrosis, oxidative stress, and the inflammasome, as well as early anti-AF therapy. Risk factor modification, such as weight loss and blood pressure control, is crucial. EAT, which is unique for its proximity to the heart and unique transcriptome and secretome, can contribute to AF through various mechanisms and is a modifiable therapeutic target. Atrial fibrosis, a central feature of ACM, can be targeted with drugs like angiotensin-converting enzyme inhibitors and beta-blockers. Oxidative stress, mediated by reactive oxygen species (ROS), can be addressed with antioxidants and NOX inhibitors. The inflammasome, particularly NLRP3, plays a role in AF pathogenesis, and selective inhibitors are being explored. Early intervention to prevent AF progression, such as antiarrhythmic drug therapy, may also be beneficial. These non-ablation approaches offer potential adjunctive therapies to improve AF outcomes.