In an era when many electrophysiologic problems are routinely treated with invasive procedures or implantable devices, drugs remain the cornerstones of treatment for atrial fibrillation. Atrial fibrillation may present as an episodic rhythm in patients who are primarily in sinus rhythm or it may be manifested as rhythm disorder that is permanent. Patients who appear to have an episodic rhythm disorder may be found to be in atrial fibrillation permanently when followed for long periods of time, and prognosis in the two forms is similar. It is, therefore, useful to consider them different manifestations in the same spectrum of disease. This review will address pharmacologic approaches designed to: (1) slow ventricular response; (2) restore sinus rhythm; (3) reduce occurrences of atrial fibrillation; and (4) prevent thromboembolic complications. Nonpharmacologic approaches to treating atrial fibrillation will be briefly reviewed.