Proton-pump inhibitors (PPIs) represent a major therapeutic advance in the management of acid-related disorders, including gastro-oesophageal reflux disease (GERD) and non-variceal upper gastrointestinal (GI) bleeding, but there still remain unmet needs, which if addressed could improve treatment. The delayed-release PPIs have quite similar pharmacokinetic and pharmacodynamic profiles. Their absorption and onset of action is delayed because they require an enteric-coating as protection against acid degradation in the stomach. To achieve maximum acid inhibition, they all need to be dosed before meals, a time when parietal cells are stimulated. Despite their remarkable ability to suppress acid during the day, delayed-release PPIs do not predictably control acid at night even when dosed twice daily. These characteristics have resulted in several unmet clinical needs specifically relating to inadequate control of nocturnal reflux symptoms, delayed symptom relief with on-demand dosing and suboptimal efficacy in those who forget or do not take their medication before eating. Immediate-release omeprazole [(IR-OME) Zegerid powder for oral suspension; Santarus Inc., San Diego, CA, USA] does not require an enteric-coating because of its unique formulation, which incorporates acid buffering sodium bicarbonate. This facilitates more rapid drug absorption, a quicker onset of action, and superior acid suppression during the night when given at bedtime. The rapid absorption and onset of action of immediate-release omeprazole also makes the medication ideally suited for those who might not comply with mealtime dosing of PPIs or who choose to manage their reflux symptoms with on-demand therapy. In addition, the immediate and prolonged acid suppression seen with single, daily, enteral dosing of immediate-release omeprazole in critically ill patients suggests this formulation is an appropriate alternative to parenteral histamine H2-receptor antagonists (H2RAs) for preventing stress related mucosal bleeding. A group of experts was convened to reflect on current management approaches to GERD and upper GI bleeding. Open discussion centred on current diagnosis and treatment, unmet needs, and strategies to meet these needs with the hope of improving management for the future. I was pleased to moderate this session and trust you will find the comments of these experts as provocative and interesting as I did. Also, I hope the summaries of the discussions presented in this publication prove useful in your day-to-day management of patients.