BACKGROUND More attention has been paid to the eradication therapy of Helicobactor pylori with the enhancement of health awareness of patients. However, the increasing antibiotic resistance of H. pylori, due to the wide use and abuse of antibiotics, has become a critical factor affecting the efficacy of eradication. To effectively improve the eradication rate of H. pylori, high-dose amoxicillin-proton pump inhibitor (PPI) dual therapy has recently become one of the hot issues. METHODS The authors review the schemes and efficacy of high-dose amoxicillin-PPI dual therapies in eradication of H. pylori infection. The review indicates that the H. pylori eradication rate of the dual therapy is overall comparable to or better than that of bismuth-containing quadruple therapy or standard triple therapy. It is more effective to administer both amoxicillin and PPI 3-4 times daily for 14 days in the high-dose amoxicillin-PPI dual therapy, and esomeprazole seems to be superior to other PPIs. CONCLUSIONS The high-dose amoxicillin-PPI dual therapy is currently a promising H. pylori eradication regimen in clinical practice, deserving further verification and discussion. Much more attention should be paid to the influence of CYP2C19 polymorphisms and virulence genotyping on H. pylori eradication, and the homogeneity and objectivity of the comparison among different studies.