Over 300 years ago the father of microscopy, Antonie van Leeuwenhoek, observed dried rotifers (tiny animals) "coming back to life" upon rehydration. Since then, scientists have been fascinated by the enduring mystery of how certain organisms survive losing essentially drying out completely. Historically sugars, such as the disaccharide trehalose, have been viewed as major functional mediators of desiccation tolerance. However, some desiccation tolerant organisms do not produce this sugar, hinting that additional mediators, and potentially novel mechanisms exist. It has become apparent that a common theme among such organisms is the production and use of intrinsically disordered proteins (IDPs) to mediate survival in this dry state. However, the basic biology of these proteins?-?which unlike globular proteins lack persistent three-dimensional structure?-?is poorly understood, as are the functional mechanisms utilized by these enigmatic proteins that allow them to mediate desiccation tolerance. We purpose that probing the biochemical and biophysical nature of stress-related IDPs will provide mechanistic insights into these fascinating proteins.