Since its first isolation by Marshall and Warren, Helicobacter pylori (H. pylori) has been recognized to have a causal role in the upper gastrointestinal diseases development, especially in chronic gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue (MALT lymphoma) and gastric adenocarcinoma. H. pylori is a spiral-shaped gram-negative flagellate bacterium that has a high genetic diversity, which is an important factor in its adaptation to the host stomach and also for the clinical outcome of the infection, an aspect that remains unclear. However, it is thought to involve a interplay among the virulence of the infecting strain, host genetics and environmental factors. This review chapter brings the principal characteristics of the diseases associated with H. pylori infection and summarizes some important characteristics concerning the virulence of bacterium strain, host genetics and external environment.