Gastric cancer is a challenging public health concern worldwide and remains a leading cause of cancer-related mortality. The primary risk factor implicated in gastric cancer development is infection withHelicobacter pylori.H. pyloriinduces chronic inflammation affecting the gastric epithelium, which can lead to DNA damage and the promotion of precancerous lesions. Disease manifestations associated withH. pyloriare attributed to virulence factors with multiple activities, and its capacity to subvert host immunity. One of the most significantH. pylorivirulence determinants is thecagPAIgene cluster, which encodes a type IV secretion system and the CagA toxin. This secretion system allowsH. pylorito inject the CagA oncoprotein into host cells, causing multiple cellular perturbations. Despite the high prevalence ofH. pyloriinfection, only a small percentage of affected individuals develop significant clinical outcomes, while most remain asymptomatic. Therefore, understanding howH. pyloritriggers carcinogenesis and its immune evasion mechanisms is critical in preventing gastric cancer and mitigating the burden of this life-threatening disease. This review aims to provide an overview of our current understanding ofH. pyloriinfection, its association with gastric cancer and other gastric diseases, and how it subverts the host immune system to establish persistent infection.