Helicobacter pylori is a significant public health concern given its high prevalence, growing rates of antibiotic resistance, and carcinogenic effect, all of which create management challenges for internists, gastroenterologists, and other specialty physicians. With almost half of the world's human population harboring H pylori, carcinogenic sequelae are a concern to many practitioners. Recent guidelines recommend testing high-risk populations for H pylori using noninvasive or invasive methods. H pylori eradication regimens are tailored based on the presence of effective empiric therapy (local cure rates ≥ 90% for a given regimen) or antimicrobial susceptibility testing. When empiric therapy cure rates are not optimal, guidelines recommend antimicrobial susceptibility testing to improve eradication rates and reduce the progression of antibiotic resistance.