Until recently, the mainstay of treatment for Helicobacter pylori infection was either dual therapy, using omeprazole with amoxycillin or clarithromycin, or traditional triple therapy comprising bismuth and two antibiotics. Success with these treatment strategies has, however, varied widely between centres. Furthermore, the side-effects reported for bismuth triple therapy and the 2-week treatment period recommended have limited its popularity. These drawbacks have thus stimulated research aimed at identifying better drug combinations, with a simpler dosage for a shorter period, fewer side-effects, and greater and more consistent efficacy. A number of studies have now been undertaken using an acid inhibitor in combination with two antibiotics. Omeprazole, a highly effective acid pump inhibitor, has been investigated most extensively in this context, and is markedly effective in eradicating H. pylori when combined with any two of clarithromycin, a nitroimidazole and amoxycillin. These omeprazole triple therapy combinations provide eradication rates that are usually in the range of 85-95%, when assessed on a per protocol basis. Side-effects are minor and rarely interfere with compliance. Increasingly, these combinations are being given in a twice-daily dosage, making them more acceptable for the patient, and the dosage of antibiotics, in some cases, can be reduced. Furthermore, 1 week of treatment has been shown to be effective. In a few patients, however, even these highly effective eradication regimens fails, and anecdotal reports suggest that, once this has happened, other treatments are often similarly ineffective. Failure is not simply a matter of antibiotic resistance because patients with resistant organisms are often cured. In some patients, poor compliance, antibiotic resistance, coccoid bacterial forms, or the presence of sanctuary sites may be the cause of failure, in others, it has been suggested that pretreatment with an acid inhibitor may be the explanation. Research into these particular areas will be required, unless a new and universally effective drug combination can be identified.