Helicobacter pylori is genetically diverse and certain strains are more virulent and cause more severe diseases than others and such diversity is reflected on the clinical outcome. The cytotoxin-associated gene (cagA) and vacuolating cytotoxin (vacA) gene are 2 putative markers that were associated with peptic ulcer disease. The basis for the epidemiological association between the cagA and vacA genes is not known. In this review, the molecular characteristics of these markers, and its role in the pathogenesis of peptic ulcer disease and gastric cancer are discussed.