The pathogenic bacterium Helicobacter pylori infects half of the human population and it is one of the most genetically diverse bacterial species known. The unusual combination of high frequencies of mutation and recombination events together with a very small size of DNA fragments imported into the genome after recombination, contribute to its genetic variability. In this review article, we discuss the genetic variability of H. pylori, the mechanisms that generate diversity, and the potential relevance of genetic variability to colonization and pathogenicity.