Selenium (Se) is a dietary essential trace element with important biological roles. Accumulating evidence indicates that Se compounds possess anticancer properties. Se is specifically incorporated into proteins in the form of selenocysteine and non-specifically incorporated as selenomethionine in place of methionine. The effects of Se compounds on cells are strictly compositional and concentration-dependent. At supranutritional dietary levels, Se can prevent the development of many types of cancer. At higher concentrations, Se compounds can be either cytotoxic or possibly carcinogenic. The cytotoxicity of Se is suggested to be associated with oxidative stress. Accordingly, sodium selenite, an inorganic Se compound, was reported to induce DNA damage, particularly DNA strand breaks and base damage. In this review we summarize the various activities of Se compounds and focus on their relation to DNA damage and repair. We discuss the use of Saccharomyces cerevisiae for identification of the genes involved in Se toxicity and resistance.