Selenium (Se) exerts its anticarcinogenic effects by multiple mechanisms. In the physiological dosage range, Se appears to function as an antimutagenic agent, preventing the malignant transformation of normal cells and the activation of oncogenes. These protective effects of Se seem to be primarily associated with its presence in the glutathione peroxidases, which are known to protect DNA and other cellular components from damage by oxygen radicals. Selenoenzymes are also known to play roles in carcinogen metabolism, in the control of cell division, oxygen metabolism, detoxification processes, apoptosis induction and the functioning of the immune system. Other modes of action, either direct or indirect, may also be operative, such as the partial retransformation of tumor cells and the inactivation of oncogenes. However, the effects of Se in the physiological dosage range are not attributable to cytotoxicity, allowing Se to be defined as a genuine nutritional cancer-protecting agent. The anticarcinogenic effects of Se are counteracted by Se-antagonistic compounds and elements. For maximal utilization of its cancer-protective potential, Se supplementation should start early in life and be maintained over the entire lifespan. In addition, exposure to Se antagonists and carcinogenic risk factors should be minimized by appropriate dietary and lifestyle changes.