Selenium occurs rarely in natural proteins, but is becoming a commonly used element in unnatural contexts to aid in the study of protein structure and function. In its natural context, selenium's role remains uncovered in half of the 25 human selenoproteins. With the aid of chemical protein synthesis, a full characterization of many of these proteins looms close on the horizon. In unnatural contexts, selenium serves as a traceless handle in native chemical ligations and as a “chaperone” for oxidative protein folding. We will discuss selenium's contributions to protein folding thus far, as well as its potential in future applications.