Atrial fibrillation is the most common cardiac dysrhythmia encountered in the primary care setting. Although a rate control strategy is pursued by physicians for the initial treatment of atrial fibrillation, the efficacy of a rhythm control approach is often undervalued despite offering effective treatment options. There are many pharmacological therapies available to patients, with drug choice often dictated by safety concerns (toxicities and proarrhythmic adverse effects) as well as patient characteristics and comorbidities. This article presents a simplified approach to understanding the rhythm control strategy, including the advantages and disadvantages of various antiarrhythmic drugs and common drug-drug interactions encountered in the primary care setting.