Catheter ablation has been proven to be an effective treatment for patients with drug-resistant atrial fibrillation. Nevertheless its efficacy is limited to 60-80% of patients in different studies. Whether the use of pharmacological therapy after catheter ablation of atrial fibrillation might increase the procedural success rate is still a matter of debate. There is general agreement that antiarrhythmic drugs (AADs) are useful in the management of arrhythmias occurring in the very early period after catheter ablation (blanking period). On the contrary, limited data are available on the efficacy of AADs over a longer period. Some patients remain free of arrhythmia recurrences by the use of AADs that were ineffective before catheter ablation: whether this latter situation is to be considered a partial success of catheter ablation or a treatment failure, thus demanding a redo procedure, is still an open question. Some studies have also investigated the role of non-AADs [angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, statins and corticosteroids] in preventing atrial fibrillation recurrences after catheter ablation, reporting conflicting results. Whereas there is a general consensus on the use of anticoagulation therapy in the first phase after catheter ablation, no definite data are available on the proper long-term management of anticoagulation therapy after catheter ablation. This review focuses on the still open issue of what is the optimal pharmacological treatment of patients after catheter ablation of atrial fibrillation.