In this article we summarise recent data published on the mechanisms involved in the complex interaction of Helicobacter pylori with the gastric mucosa as well as cellular compartments beyond the stomach. This includes the direct effect of H. pylori membrane proteins and their interplay with epithelial surface proteins, mediating cellular adhesions and facilitating colonisation. Another highly relevant factor remains the modulation of different immune cell types, not only having an effect on both local (gastric) and systemic inflammation, but also having been suggested to be relevant in the pathogenesis of non-gastric conditions such as arteriosclerosis and Alzheimer’s disease. Direct cell-cell interaction of the H. pylori stimulated gastric microenvironment, including activation of nuclear factor kappa B dependent signalling in epithelial and inflammatory cells, regulates cell proliferation and migration in the process of gastric carcinogenesis. Both host and bacterial genetic factors that influence these processes remain in the focus, but there is also increasing interest in how these factors alter the composition of not only the gastric, but also the intestinal microbiota and what effect this has on the individual. Finally, resistance of H. pylori to antibiotics has become an increasingly relevant threat since treatment failure can lead to a significant long-term risk for the patient. Hence, mechanisms involved in resistance development are a major focus of current H. pylori studies.