Oxidative stress is a disturbance in the equilibrium among free radicals, reactive oxygen species, and endogenous antioxidant defense mechanisms. Oxidative stress is a result of imbalance between the production of reactive oxygen and the biological system's ability to detoxify the reactive intermediates or to repair the resulting damage. Mounting evidence has implicated oxidative stress in various physiological and pathological processes, including DNA damage, proliferation, cell adhesion, and survival of cancer cells. Glutathione peroxidases (GPxs) (EC 1.11.1.9) are an enzyme family with peroxidase activity whose main biological roles are to protect organisms from oxidative damage by reducing lipid hydroperoxides as well as free hydrogen peroxide. Currently, 8 sub-members of GPxs have been identified in humans, all capable of reducing H2O2 and soluble fatty acid hydroperoxides. A large number of publications has demonstrated that GPxs have significant roles in different stages of carcinogenesis. In this review, we will update recent progress in the study of the roles of GPxs in cancer. Better mechanistic understanding of GPxs will potentially contribute to the development and advancement of improved cancer treatment models.