Much attention has recently been given to the role of the Helicobacter pylori CagA protein, the only as yet identified H. pylori protein that is delivered into the host gastric epithelial cells by a type IV secretion system, in the development of H. pylori-associated diseases, including gastric carcinoma. This review summarizes the latest advances in our understanding of pathogenic actions of H. pylori CagA, particularly focusing on the molecular mechanisms underlying CagA entry into the host cells as well as CagA-mediated perturbation of host cell signaling involved in proliferation, motility, differentiation, and polarity, which contributes malignant transformation of mammalian cells.