Atrial fibrillation is the most commonly encountered cardiac arrhythmia and is directly or indirectly responsible for considerable mortality, morbidity and health care burden. The available medical therapy is limited by marginal efficacy, end-organ toxicity, as well as the potential for undesired ventricular proarrhythmia. Elucidation of the potential mechanisms that underlie the development of atrial fibrillation may provide new targets for drugs that circumvent the problems associated with current medical options. This review focuses on the current and potential future pharmacological agents directed at rhythm control and maintenance of sinus rhythm.