Infection with the Gram-negative pathogen Helicobacter pylori (H. pylori ) has been associated with gastroduodenal disease and the importance of H. pylori eradication is underscored by its designation as a group I carcinogen. The standard triple therapy consists of a proton pump inhibitor, amoxicillin and clarithromycin, although many other regimens are used, including quadruple, sequential and concomitant therapy regimens supplemented with metronidazole, clarithromycin and levofloxacin. Despite these efforts, current therapeutic regimens lack efficacy in eradication due to antibiotic resistance, drug compliance and antibiotic degradation by the acidic stomach environment. Core tip: This article reviews the recent literature describing antibiotic resistance and trends in Helicobacter pylori (H. pylori ) treatment. As there is no effective conventional therapy, new treatments are being developed and bismuth quadruple, sequential, concomitant therapies are recommended as a first-line regimen in regions with high levels of clarithromycin resistance. Quinolones have also been used for H. pylori treatment, although the cure rate has gradually reduced with this approach. New therapeutic directions include probiotic supplementation, tailored therapy, novel agents, and nanotechnology.