The management of dyspepsia has been radically altered by the discovery of the role of Helicobacter pylori and the advent of proton pump inhibitors (PPIs). The use of PPIs alone as antisecretory agents and as part of triple therapy regimens for H. pylori eradication accounts for a significant percentage of any healthcare system's drug budget. Thus, it is important to take into account a variety of factors when devising a formulary and considering which PPIs to include. Consideration of 3 factors are particularly crucial in this process, namely therapeutic efficacy, tolerability and cost but several other clinical and economic parameters should also be considered. The mechanisms of action of all 4 PPIs currently available (omeprazole, lansoprazole, pantoprazole and rabeprazole) are very similar, with any small differences in pharmacological properties unlikely to be of clinical significance. Therapeutic efficacy in patients with acute reflux oesophagitis is again very similar for all 4 PPIs at their standard dosages; all agents are superior to H2-antagonists. Data on maintenance therapy for reflux oesophagitis also suggest similar efficacy for omeprazole and lansoprazole; data on pantoprazole and rabeprazole are awaited. For the treatment of H. pylori-related ulcers, the consensus at present is for PPI-based triple therapy. Again, all PPIs seem equally efficacious for this indication but pantoprazole and rabeprazole have yet to receive licences for H. pylori eradication therapy (HPET) in most countries. Drug tolerability is another critical issue to consider in formulary inclusion decisions. As a class, the PPIs are well tolerated. Minor drug interactions are reported for omeprazole, lansoprazole and rabeprazole but not for pantoprazole. However, whether or not this is significant in clinical practice is open to debate. Most of the pharmacoeconomic data in these indicators, to date, relate to omeprazole and, to a lesser extent, lansoprazole. Certainly, the studies on these 2 drugs confirm the superior cost effectiveness of PPIs over H2-antagonists in the treatment of reflux oesophagitis and peptic ulceration in both the short and long-terms. Although data are awaited, there is no reason to suggest that this will be any different for pantoprazole and rabeprazole. PPI-based triple therapy for H. pylori eradication appears to be the most cost-effective treatment option for H. pylori-related peptic ulcer disease. It is clear that PPIs are superior in several regards to previously used medications in the treatment of dyspepsia. Which PPI(s) to include in a particular formulary is a more difficult decision. On review of many criteria involved in formulary decisions, differences between the individual PPIs appear minimal. The relative acquisition costs of the PPIs vary nationally and internationally and this may be a critical factor in formulary inclusion decisions. However, one should not ignore non-economic factors, as these should form the basis of any sound drug policies.