A rhythm control strategy based on a combination of antiarrhythmic drugs and electrical cardioversion(s) has emerged as a viable alternative for treatment of atrial fibrillation, particularly when the arrhythmia is associated with symptoms, which may be poorly tolerated, or with congestive heart failure. Several classes of antiarrhythmic drugs are available to restore sinus rhythm by chemical cardioversion and to help maintain it once it has been achieved. In our discussion, we will detail aspects of their efficacy and safety, and attempt to outline a pragmatic clinical approach to their use. Some newer drugs are currently under investigation and hold promise for improved efficacy and/or more favorable side effect profile and will be mentioned in this article.