Antiarrhythmic drug therapy for cardiac rhythm control remains a therapeutic mainstay in the treatment of patients with atrial fibrillation. Currently available antiarrhythmic drugs have limited efficacy and can be associated with significant safety and tolerability issues. Many innovative drug-development strategies that target various aspects of atrial fibrillation development and maintenance are currently being explored. There are agents that target atrial repolarization (atrial repolarization delaying agents [ARDA]), and there are new antiarrhythmic drugs with more conventional antiarrhythmic mechanisms, including new multiple-channel blocking agents with better safety and tolerability profiles. Vernakalant is an example of a new ARDA-type drug, whereas dronedarone is a prototype of the new multiple-channel blocking agents. These two compounds are the most advanced novel antiarrhythmic drugs with an almost complete portfolio. Whereas vernakalant is predominantly developed for pharmacological cardioversion of atrial fibrillation, dronedarone can stabilize sinus rhythm after cardioversion and does control the ventricular rate in case of recurrent atrial fibrillation. This review summarizes the current status of development of novel antiarrhythmic compounds to be used for therapy of atrial fibrillation.