Helicobacter pylori, a major stomach pathogen associated with gastritis, gastric/duodenal ulcer, gastric cancer and other diseases, shows extreme diversity at the genome sequence level. It is now possible to sequence whole genomes of Japanese isolates at a reasonable cost. Here I summarize what has been learned from analyzing whole H. pylori genomes. Emphasis is placed on features of East Asian strains, genome dynamics and epigenetics. I cover both long-term evolution with us Homo sapiens and short-term evolution within our bodies. I hope this guide will be helpful for decoding and analyzing H. pylori genomes of clinical isolates, especially those from Japan and other East Asian countries.