The discovery of (Helicobacter pylori) H. pylori by Warren and Marshall in 1982 was preceded by nearly a hundred year of inconspicuous publications in regard to spiral bacteria, achlorhydria, gastritis, gastric urease, and antimicrobial therapy for peptic ulcers. The infection has now been implicated in the etiopathogenesis of chronic gastritis, peptic ulcer disease (PUD), gastric carcinoma, and gastric mucosal associated lymphoid tissue (MALT) lymphoma. The understanding of the etiopathogenesis of dyspepsia and the approach to its management continues to evolve such that PUD and MALT lymphoma are now being considered as infectious diseases in which elimination of the causative agent cures the conditions. Various diagnostic tests with good diagnostic accuracies have been developed and effective multiple antimicrobial therapies are now available for the eradication of the infection. Despite the substantial progress made, there still exits a considerable gap to be filled. A significant number of information generated from studying the bacterial characteristics and host response to the infection has not yet been translated into clinical practice. A major challenge is the absence of a specific antibiotic monotherapy for effective treatment of the infection.