Selenium is an oligoelement with essential biological functions. Diet is the most important selenium source, and intake of this element depends on its concentration in food and amount of food consumed. Among the essential human micronutrients, selenium is peculiar due to its beneficial physiological activity and toxicity. It may have anticarcinogenic effects at low concentrations, whereas at concentrations higher than those necessary for nutrition, it can be genotoxic and carcinogenic. Because of that, selenium is probably the most widely investigated of all the oligonutrients. In the last decades, there has been increasing interest in several nutritional Se compounds because of their environmental, biological, and toxicological properties, particularly for their cancer- and disease-preventing activities. This article gives an overview of the results of in vitro studies on mutagenicity, genotoxicity, cytotoxicity, and DNA repair conducted within the last decades with different organic and inorganic selenium compounds. Results from these studies provide a better knowledge on the selenium activity and help to elucidate the reasons underlying its duality in order to regulate its correct use in nutrition and clinic.