Helicobacter pylori is a human-specific pathogen that chronically infects about 50% of the world s population. After travelling through the harsh environment of the stomach lumen, H. pylori colonizes the mucosal surface and within the glands of the human stomach. During colonization, H. pylori uses motility and its chemotaxis signalling system to sense the environment to reach the gastric epithelium for colonization, where it is able to attach to the epithelial surface. The H. pylori population inside the stomach contains a subgroup of bacteria that are attached to the gastric epithelium and a larger subgroup of non-attached bacteria that are freely swimming. To establish a tight interaction between H. pylori and epithelial cells, the bacterium produces a variety of adhesins and delivers virulence factors. These lead to alterations in the host signalling pathways, inducing pro-inflammatory responses, apoptosis, uncontrolled cell proliferation, and eventually peptic ulcers and gastric cancer. To prevent disease and find a vaccine or better treatments, it is crucial to understand how H. pylori is able to sense its niche for chronic infection inside the stomach and how its virulence factors interact with the epithelial target cells.