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 Ca(2+) 
handling in AF and targeting atrial remodeling.