Helicobacter pylori is a Gram-negative bacterium that colonizes the human stomach and is considered as the primary risk factor for the development of gastroduodenal pathology, such as gastric cancer and gastric MALT lymphoma. The bacteria-mediated pathogenesis is governed by an interplay between its virulence factors and genetic polymorphisms of the host, as well as environmental factors. Gastric inflammatory response has been characterized as the key element that promotes disease, however, additional new knowledge on underlying mechanisms related to the deregulation of numerous host biological processes have been shown to contribute to pathogenesis over the last 35 years. The present review summarizes some of the most important studies published between April 2020 and March 2021 offering further insight on how H. pylori infection can perturb host biological processes such as immune response, gene expression, genome maintenance, cell proliferation, survival and death, as well as the microbiota profile, thus inducing pathogenesis.