Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia and has a significant impact on morbidity and mortality. Current antiarrhythmic drugs for AF suffer from limited safety and efficacy, probably because they were not designed based on specific pathological mechanisms. Recent research has provided important insights into the mechanisms contributing to AF and highlighted several potential novel antiarrhythmic strategies. In this review, we highlight the main pathological mechanisms of AF, discuss traditional and novel aspects of atrial antiarrhythmic drugs in relation to these pathological mechanisms, and present potential novel therapeutic approaches including structure-based modulation of atrial-specific cardiac ion channels, restoring abnormal Ca²⁺ handling in AF and targeting atrial remodeling.