Gastric cancer remains the second most common cause of cancer-related mortality worldwide. The single most common cause of gastric cancer is chronic infection with the gram-negative microaerophilic spiral bacterium: Helicobacter pylori. Recent advances in this field have identified host factors which predispose to gastric cancer formation via modulation of the host immune response. In addition, recent work has explored bacterial virulence factors which may directly cause tissue damage, and lead to gastric carcinogenesis, as well as factors responsible for enhanced immune response. Environmental factors, long associated with a predilection for gastric cancer, are recognized as modifiers of key growth signalling pathways within the gastric mucosa and as such lead to growth alterations. This review focuses on exploring new advances in our understanding of bacterial factors, host genetic polymorphisms and the interaction between the bacterium and host at the level of the immune response and the regulation of proliferative and apoptotic signal transduction cascades. Modulation of the pivotal balance between cell growth and cell death leads to the formation of gastric adenocarcinoma.