Atrial fibrillation (AF) is the most common cardiac arrhythmia with a prevalence ranging from 5% over 60 years old to 17% after 85 years old. Besides hemodynamical compromises and occurrence of heart failure, stroke remains the most feared complication related to AF with a risk increased by 5-fold. Catheter ablation with the aim of pulmonary veins isolation (PVI) has evolved as a standardized treatment option in paroxysmal AF (PAF), supported by the current guidelines. However, due to advanced electrical and structural remodeling, catheter ablation for persistent AF is rather disappointing with a limited success rate, at least after a single procedure. Due to these shortcomings, minimally invasive thoracoscopic surgical techniques have gained attention with good results in persistent AF patients. Comparison between thoracoscopic surgical ablation and catheter ablation have shown that surgical ablation was associated with higher success rates, less redo procedures but also with higher complication rates. The main issue with surgical ablation is the difficulty to check the ablation lines and pulmonary vein isolation, which are the cornerstones for achieving good long-term results. Hybrid therapy, combining both epicardial surgical and endocardial catheter ablation is expected to be the most effective technique. It would avoid incomplete lesions or incomplete pulmonary vein isolation, and would provide complete lesion set. Hybrid therapy of AF has been compared with mini-invasive surgical ablation of AF, showing a significant higher rate of sinus rhythm achievement in the hybrid therapy group. However, no comparative clinical trials data are currently available in the setting of persistent AF comparing hybrid ablation and conventional catheter ablation.