Abstract Objective Recent guidelines by the National Institute for Health and Clinical Excellence (NICE) and the American College of Cardiology/American Heart Association/European Society of Cardiology (ACC/AHA/ESC) on rate control management for chronic atrial fibrillation have relegated digoxin to second line treatment, recommending instead the use of β-blockers or rate limiting calcium antagonists as first line treatment. The objective of this review is to assess the efficacy of these drugs in controlling heart rate, and in improving symptoms and exercise tolerance. Data sources We electronically searched the Medline, Embase and Cochrane databases, hand searched journals and relevant bibliographies for articles. Selection of studies We included all study designs evaluating or comparing oral digoxin, β-blockers and calcium antagonists, alone or in combination, for rate control in chronic atrial fibrillation. 46 studies satisfied our inclusion and quality criteria. Results Published studies are small and too heterogeneous to be quantitatively combined. Descriptive synthesis of the data shows little evidence that monotherapy with β-blockers or calcium antagonists improves symptoms or exercise capacity in patients with chronic atrial fibrillation. Instead it is associated with dose related side effects. Conclusion Based on the limited data available, we conclude that the combination of digoxin with either a β-blocker or calcium antagonist should be first line management in patients with chronic atrial fibrillation.