Gastric cancer is a global health threat and contributes to more than 800,000 deaths per year. Helicobacter pylori is now recognized as the main risk factor that initiates this process; hence, H. pylori eradication has been considered the most effective method to ameliorate the burden of gastric cancer. In the setting of mass screening, the expense of testing for and treating H. pylori, the optimal regimen for targeting the asymptomatic population within the community remains unclear. Besides, the risk of treatment side effects, and increasing prevalence of antibiotic resistance among H. pylori virulent strains constitute important challenges to potential eradication programs. Therefore, it is crucial to survey the pattern of antibiotic resistance of H. pylori via community evidence before the implementation as the national policy. While gastric cancer is extremely rare where H. pylori prevalence is very low, the opposite is not always true. Several explanations have been proposed for the paradox of places with high prevalence of infection and low gastric cancer incidence, including differences in pathogenicity factors of different strains of H. pylori present in the different areas, diet and salt consumption, genetic susceptibility, presence of other infections, and the interaction of all these factors, but none of them has been proved. The availability of the complete genome sequences of different H. pylori strains will have profound impact on all the aspects of research from the basic biology of H. pylori and its identification of virulence factors to the development of new therapeutic strategies for eradication of this organism.