Two model systems for examining the role of selenoproteins in health are discussed. One utilizes transgenic mice that carry mutant selenocysteine (Sec) tRNA transgenes that result in the reduction of selenoprotein expression in a protein- and tissue-specific manner. The other utilizes loxP-Cre technology to selectively remove the Sec tRNA gene in mammary epithelium that results in the reduction of only certain selenoproteins in this tissue. Both approaches provide important tools for examining the role of selenoproteins in health.