The eradication rates of Helicobacter pylori by the triple therapy consisting of a proton pump inhibitor (PPI) and two antimicrobial agents are mainly influenced by bacterial susceptibility to antimicrobial agents and magnitude of acid inhibition during the treatment with a PPI. Acid inhibition during the treatment is affected by the dosing schemes of acid inhibitory drugs (i.e., PPI), genotypes of drug-metabolizing enzymes (i.e., CYP450 2C19), drug transporters (i.e., multi-drug resistant transporter-1) and inflammatory cytokines (i.e., IL-1 beta). Modification of dosing schedules of a PPI, such as frequent PPI dosing and concomitant dosing with a histamine 2-receptor antagonist, could overcome these genetics-related differences in therapeutic effectiveness. For attaining higher eradication rates, the tailored regimen based on the relevant pharmacogenomics is preferable.