The origin and persistence of AF result from a complex interaction between triggers, autonomic nervous system, substrate, and factors involved in atrial remodelling. The pathophysiology of AF differs from one patient to another, but recent advances have helped us to understand more about involved mechanisms and to translate this knowledge into improvements in AF therapy. An illustration is the elimination of triggers within pulmonary veins by means of catheter ablation. Dealing with structural atrial remodelling and atrial fibrosis remains still a great challenge. Solving these problems could help us to develop new approaches to AF prevention and treatment.