Catheter ablation is an established treatment option for patients with atrial fibrillation (AF). In paroxysmal AF ablation, pulmonary vein isolation alone is a well-defined procedural endpoint, leading to success rates of up to 80% with multiple procedures over 5 years of follow-up. The success rate in persistent AF ablation is significantly more limited. This is partly due to the rudimentary understanding of the substrate maintaining persistent AF. Three main pathophysiological concepts for this arrhythmia exist: the multiple wavelet hypothesis, the concept of focal triggers, mainly located in the pulmonary veins and the rotor hypothesis. However, the targets and endpoints of persistent AF ablation are ill-defined and there is no consensus on the optimal ablation strategy in these patients. Based on these concepts, several ablation approaches for persistent AF have emerged: pulmonary vein isolation, the stepwise approach (i.e. pulmonary vein isolation, ablation of fractionated electrograms and linear ablation), magnetic resonance imaging (MRI) and rotor-based approaches. Currently, persistent AF ablation is a second-line therapy option to restore and maintain sinus rhythm. Several factors, such as the presence of structural heart disease, duration of persistent AF and dilatation and possibly also the degree of fibrosis of the left atrium should influence the decision to perform persistent AF ablation.