Core tip: There has been a significant decrease in the success rate of empirical triple therapy to treat Helicobacter pylori (H. pylori) infection, largely due to a rapid increase in the prevalence of antibiotic resistant strains. Antibiotic resistance is a constantly evolving process and there are significant regional variations in H. pylori antibiotic resistance rates. As such, local surveillance of antibiotic resistance is warranted to guide clinicians in their therapeutic choice. Standard culture-based antimicrobial susceptibility testing and molecular methods provide key opportunities to tailor H. pylori treatment based on the detection of antibiotic resistant strains, thereby enhancing eradication rates and decreasing H. pylori-associated disease.