Helicobacter pylori (H. pylori) is one of the most important human pathogens, infecting approximately half of the global population. Despite its high prevalence, only a subset of H. pylori infected individuals develop serious gastroduodenal pathology. The pathogenesis of H. pylori infection and disease outcome is thus thought to be mediated by an intricate interplay between host, environmental and bacterial virulence factors. H. pylori has adapted to the harsh milieu of the human stomach through possession of various virulence genes that enable survival of the bacteria in the acidic environment, movement towards the gastric epithelium, and attachment to gastric epithelial cells. These virulence factors enable successful colonization of the gastric mucosa and sustain persistent H. pylori infection, causing chronic inflammation and tissue damage, which may eventually lead to the development of peptic ulcers and gastric cancer. Numerous studies have focused on the prevalence and role of putative H. pylori virulence genes in disease pathogenesis. While several virulence factors with various functions have been identified, disease associations appear to be less evident, especially among different study populations. This review presents key findings on the most important H. pylori virulence genes, including several bacterial adhesins and toxins, in children and adults, and focuses on their prevalence, clinical significance and potential relationships.