This article reviews current evidence of non-antiarrhythmic agents for the prevention and maintenance of sinus rhythm in patients with atrial fibrillation. These nontraditional agents include angiotensin converting enzyme inhibitors, angiotensin receptor blockers, antiinflammatory agents, calcium channel blockers, and beta-blockers. The mechanisms of action and clinical trials regarding the effectiveness of these agents in atrial fibrillation prevention are reviewed.