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Since the discovery of Helicobacter pylori in the early 1980s many treatment regimes have been developed to effectively treat this infection. International guidelines have allowed consensus on the best management and improved eradication rates. In recent years, increasing antimicrobial resistance has resulted in falling eradication rates with standard therapies. In this article, we review the most recent studies and guidelines in the treatment of H. pylori. Currently, the first-line treatment remains clarithromycin, amoxicillin or metronidazole and proton pump inhibitor twice daily, but a number of recent studies have shown low eradication rates with this treatment. Increased duration of therapy has been recommended to overcome the falling eradication rates. However, conflicting findings have been reported on the benefits of extending the length of traditional therapy. Sequential therapy may be an effective alternative to standard triple therapy in regions of increased antimicrobial resistance. Probiotics reduce side-effects from traditional regimens and may improve eradication rates. A quinolone-based second-line triple therapy appears to be effective and well tolerated. Bismuth-based quadruple therapy is also an effective alternative if available. In the future, regional antimicrobial resistance and eradication rates will determine the best treatment for H. pylori.