Although gastric acid secretion is usually normal in patients with gastroesophageal reflux disease (GERD), treatment with proton pump inhibitor (PPIs) has become the standard of care. However, despite their effectiveness, PPIs display some intrinsic limitations, which underlie the unmet clinical needs that have been identified over the past decades in the treatment of acid-related diseases. In GERD, these include an increased ability to control acid secretion and symptoms (particularly at night), an inproved healing of severe erosive esophagitis as well as an effective management of extra-esophageal manifestations. To address these needs, several drug classes or combinations have been developed. However, a major advance has been the development of the potassium-competitive acid blockers (P-CABs), which block the K+,H+-ATPase K+ channel, are food independent, reversible, display a rapid onset of action and maintain a prolonged and consistent elevation of intragastric pH. Vonoprazan and tegoprazan are the two marketed P-CABs while two other compounds (namely fexuprazan and X842) are under active development. Available for almost 6 years now, a considerable experience has been accumulated with vonoprazan, the efficacy of which in erosive reflux disease will be discussed in details. P-CABs clearly overcome many of the drawbacks and limitations of the delayed-release PPIs. In GERD, mucosal healing is directly related to the degree and duration of acid suppression as well as the length of treatment. As a consequence, compared with the currently available PPIs, vonoprazan with its rapid, potent and prolonged acid suppression achieves fast and assured healing of severe reflux esophagitis as well as rapid heartburn relief. In addition, even at half the dose, this P-CAB was significantly more effective than standard dose PPI in maintaining C & B esophagitis in remission. The unique antisecretory effects of vonoprazan might be especially useful in the long-term treatment of patients with Barrett’s esophagus.