The mainstay of catheter ablation for atrial fibrillation (AF) is pulmonary vein isolation (PVI). The shortcomings of a point-by-point ablation approach using radiofrequency current steadily kindle the interest in new energy sources and catheter designs. The most promising currently available techniques are balloon catheters using cryothermal energy (CRYO) or high-intensity focused ultrasound (HIFU). Both technologies have proven to be efficacious. However, for both technologies treatment strategies have to be developed to overcome the relatively high incidence of collateral damage such as phrenic nerve palsy or atrial-to-esophageal fistula. The results for patients with persistent AF in whom substrate modification is considered beneficial are poor and limit the use of balloon-based PVI to patients with paroxysmal atrial fibrillation (PAF). Moreover, based on the individual anatomy more than one balloon size may be required or may even make balloon-based PVI impossible in certain patients.