Although Helicobacter pylori infects 50% of the total human population, only a small fraction of the infected people suffer from severe diseases like peptic ulcers and gastric adenocarcinoma. H. pylori strains, host genotypes and environmental factors play important role in deciding the extent and severity of the gastroduodenal diseases. The bacteria has developed a unique set of virulence factors to survive in the extreme ecological niche of human stomach. Together these virulence factors make H. pylori one of the most successful human pathogenic bacteria colonizing more than half of the human population. Understanding the mechanism of action of the major H. pylori virulence factors will shed light into the molecular basis of its pathogenicity.