SUMMARYEsomeprazole, the S‐isomer of omeprazole, is the first proton pump inhibitor synthesised as an optical isomer to become available for clinical use. Esomeprazole is optically stable in humans with negligible inversion to the R‐isomer. Esomeprazole has significantly higher oral bioavailability than omeprazole, resulting in greater acid suppression. In clinical studies, 4 weeks' treatment with 40 mg esomeprazole demonstrated greater healing of all grades of erosive oesophagitis, compared with 20 mg omeprazole (76–82% versus 69–71%) and higher rates of symptom resolution (65–68% versus 58–61%) Furthermore, esomeprazole maintained healing rates of up to 90% over 6 months in erosive oesophagitis. Comparisons with other proton pump inhibitors in oesophagitis are, as yet, unavailable. In patients with endoscopy‐negative gastro‐oesophageal reflux disease (GERD), on‐demand therapy with esomeprazole 20 mg has been shown to be very efficacious compared with placebo, and is well tolerated; however, comparisons with other proton pump inhibitors have not been performed. Long‐term use of esomeprazole for up to 12 months in patients with GERD have not raised any significant safety concerns with respect to the development of atrophic gastritis or clinically relevant changes in enterochromaffin‐like cells.