The article by Martin J. Blaser and John C. Atherton discusses the complex relationship between *Helicobacter pylori* and humans, focusing on the bacteria's persistence in the stomach and its impact on human health. *H. pylori* has coevolved with humans, colonizing the stomach and maintaining a dynamic equilibrium with the host. This equilibrium is maintained through a series of mechanisms that allow the bacteria to adapt to the host environment and vice versa. The article highlights two key domains of interaction: the cag island, which encodes a protein (CagA) that interacts with epithelial cells, and the vacA gene, which encodes a pore-forming protein (VacA) that affects gastric physiology. These interactions can lead to both protective and pathogenic effects, such as the induction of antiapoptotic pathways and immune suppression, respectively. The authors also explore the immune response to *H. pylori* and its role in disease. The immune system's activation following infection can lead to chronic inflammation and atrophic changes in the stomach, which are risk factors for peptic ulcer disease and gastric cancer. The topographic distribution of inflammation, whether antral-predominant or pan-gastritis, influences acid homeostasis and disease outcomes. Additionally, the article discusses the potential benefits of *H. pylori* colonization, such as enhanced protection against diarrheal pathogens, and its possible role in human evolution. Finally, the article examines the carcinogenic effects of *H. pylori*, suggesting that chronic inflammation and DNA damage may contribute to gastric carcinogenesis. The authors propose that carcinogenesis could be a mechanism by which *H. pylori* contributes to the fitness of premodern human populations by removing senescent individuals. The article concludes by emphasizing the need to understand the complex interactions between *H. pylori* and the host to develop effective interventions and vaccines.The article by Martin J. Blaser and John C. Atherton discusses the complex relationship between *Helicobacter pylori* and humans, focusing on the bacteria's persistence in the stomach and its impact on human health. *H. pylori* has coevolved with humans, colonizing the stomach and maintaining a dynamic equilibrium with the host. This equilibrium is maintained through a series of mechanisms that allow the bacteria to adapt to the host environment and vice versa. The article highlights two key domains of interaction: the cag island, which encodes a protein (CagA) that interacts with epithelial cells, and the vacA gene, which encodes a pore-forming protein (VacA) that affects gastric physiology. These interactions can lead to both protective and pathogenic effects, such as the induction of antiapoptotic pathways and immune suppression, respectively. The authors also explore the immune response to *H. pylori* and its role in disease. The immune system's activation following infection can lead to chronic inflammation and atrophic changes in the stomach, which are risk factors for peptic ulcer disease and gastric cancer. The topographic distribution of inflammation, whether antral-predominant or pan-gastritis, influences acid homeostasis and disease outcomes. Additionally, the article discusses the potential benefits of *H. pylori* colonization, such as enhanced protection against diarrheal pathogens, and its possible role in human evolution. Finally, the article examines the carcinogenic effects of *H. pylori*, suggesting that chronic inflammation and DNA damage may contribute to gastric carcinogenesis. The authors propose that carcinogenesis could be a mechanism by which *H. pylori* contributes to the fitness of premodern human populations by removing senescent individuals. The article concludes by emphasizing the need to understand the complex interactions between *H. pylori* and the host to develop effective interventions and vaccines.