The finding of the bacterium Helicobacter pylori in patients with symptomatic gastric diseases was a breakthrough for both treatment of peptic ulcer disease and studies of other infectious diseases. Helicobacter pylori infection is rare among the young, indicating that improved childhood living conditions have halted the transmission of the bacterium within families, with a parallel decrease in symptomatic gastroduodenal diseases. Extensive strain variation in H. pylori has been demonstrated at both the genomic and the protein level, and the interstrain variation is higher than in any other bacterium studied so far. Pathogenic markers in H. pylori and host genetics are both of importance for disease outcome. Genotypic or phenotypic markers of H. pylori strains may be used to discriminate patients who should undergo eradication therapy from those who might not benefit from it. Possible positive effects of the infection are still under investigation, and several hypotheses regarding the etiology of diseases in different parts of the stomach have been proposed. To be able to separate the disease-causing infections from the silent infections is a real challenge for the new millennium, and one of the most important issues for therapy and prevention, in the research field of H. pylori.