Rabeprazole is a proton pump inhibitor. Pharmacodynamic data show rabeprazole can achieve optimal acid suppression since the first administration and can maintain this advantage in the following days of therapy. Moreover, rabeprazole has the highest pKa (~ 5.0, the pH at which a drug becomes 50% protonated), and hence the molecule can be activated at higher pH levels much faster than other PPIs. Due to its peculiar catabolic pathway, ie, a prevalent metabolism through a non-enzymatic pathway, rabeprazole is less susceptible to the influence of genetic polymorphisms for CYP2C19, resulting in minor influences on its pharmacokinetics and pharmacodynamics. In terms of clinical efficacy, rabeprazole 20 mg uid or 10 mg bid produced healing rates at 8 weeks similar to those obtained with omeprazole 20 mg uid in erosive esophagitis patients, and in NERD patients doses of 10 or 20 mg are equivalent and both are better than placebo at 2 and 4 weeks. To prevent symptomatic relapse, on-demand strategy with rabeprazole 10 mg daily appears to be ideal, due to its rapidity of onset; results on NERD patients have documented its superiority over placebo. Continuous treatment, however, up to 5 years, seems to achieve better results than on-demand therapy, particularly in patients with esophagitis. It is debated whether in the latter halved doses (10 mg) are really equivalent to full dose (20 mg). Rabeprazole has been used with success in the treatment of some atypical GERD manifestations, such as dysphagia associated with GERD, GERD-related asthma and chest-pain, and in the therapy of Barrett's esophagus. Finally, rabeprazole achieves similar Helicobacter pylori eradication rates compared with omeprazole and lansoprazole when co-administrated with low or high doses of antibiotics (amoxicillin and clarithromycin). In addition, low doses of rabeprazole (10 mg/bid) may be effective in eradicating the pathogen.