Gastroesophageal reflux disease (GERD) is increasingly common worldwide; symptoms differ between individuals and endoscopically visible injury is present in only about 50% of cases. Although GERD is a disorder of gastrointestinal motility and structure, the most effective therapy is based on the use of acid antisecretory drugs. Proton pump inhibitors (PPIs), the most effective class of acid suppression agents to date, have revolutionised the management of GERD. However, PPIs do have some shortcomings and recent developments include documentation of increased healing rates with more prolonged acid suppression, more prolonged acid suppression with a new PPI (tenatoprazole) and more rapid onset of acid suppression with a new class of drugs, the reversible, potassium-competitive acid blockers. Studies with motility agents, such as the 5-HT(4) partial agonist tegaserod and the GABA(B) agonist baclofen, indicate that motility is important in the pathogenesis of GERD but, for several reasons, it will be a challenge to develop new classes of drug that outperform current PPIs with respect to efficacy, broad applicability and safety.