The efficacy of established Helicobacter pylori regimes needs to be reviewed. In view of drug resistance, side effects, and compliance and expense of therapy, treatment failure is increasing and second-line treatment strategies need to be developed. A simulation model suggested by the Cochrane review group showed that H. pylori eradication is cost-effective for duodenal and gastric ulcer long-term. The duration of eradication therapy continues to be controversial. In Europe and other parts of the world, 7-day triple regimes are used, whereas guidelines from the United States recommend 10-14 days of therapy. Antibiotic resistance is a major factor affecting the outcome of eradication therapy. New modified eradication regimes involve substitution of antibiotics used in conjunction with other drugs. The newer generation fluoroquinolones have shown some promise as part of an eradication regimen. Quadruple therapy (bismuth, proton pump inhibitor [PPI] and two antibiotics and sequential treatment [PPI with three antibiotics]) are promising first-line treatments. Novel agents have been tried, but with disappointing results. New drugs and administration forms have been reported but their efficacy needs confirmation.