The updated prevalence of H. pylori infection is 30% in adults and 8-10% in children and adolescents in a nationwide survey in Taiwan during 2019-2020. The prevalence of antibiotic resistance of clarithromycin, levofloxacin, metronidazole, amoxicillin, and tetracycline in adults are 16%, 18%, 24%, 2%, and 5%, respectively, in Taiwan. Personalized treatment guided by susceptibility testing may provide a reliably excellent eradication rate in the first-line treatment but is costly and not widely available. Population-specific empirical therapy according to the local prevalence of antibiotic resistance may be an alternative strategy. Bismuth quadruple therapy is recommended in regions with high clarithromycin resistance (15-20%). Clarithromycin-based non-bismuth quadruple therapy (sequential, concomitant or hybrid therapy) may be an acceptable alternative in regions with clarithromycin resistance rate lower than 20%. High dose dual therapy with amoxicillin (3gm/day) and proton pump inhibitor (omeprazole 20mg or equivalent dose three to four times a day) is a potential regimen in the first-line therapy. Levofloxacin-based therapy should be reserved for second-line and third-line rescue therapies. Bismuth quadruple therapy and 14-day levofloxacin containing sequential therapy are similarly effective in the second-line treatment of H. pylori infection. Susceptibility testing or genotypic resistance-guided therapy is the preferred treatment for refractory H. pylori infection, but empirical therapy may be an acceptable alternative. Rifabutin based therapy may be used in the fourth-line rescue therapy for refractory H. pylori infection.