Solid-state proteins are typically formulated with sugars or polyols to enhance stability, with the primary assumption that these carbohydrate molecules contribute to stabilizing the protein structure or rigidity of the molecular dynamics. There are two well recognized hypotheses for how these additives stabilize the dry-state protein during drying and storage. The first hypothesis is the water replacement theory, and the other is glass dynamics or the so-called vitrification theory. The former is a thermodynamic stabilization mechanism while the latter is from the kinetic perspective. A schematic illustration of these theories is presented in Figure . It is worth noting that although protein stability is often discussed in either one of the theories or the two mechanisms can contribute to protein stabilization simultaneously. In addition, the mechanism of stabilization can be protein specific though the same salt or sugar stabilized is used. Nguyen et al. showed that lactate dehydrogenase (LDH) stabilization in the sugar matrix requires vitrification whereas β-galactosidase (β-gal) can partly retain structural stability in the rubbery state. The difference in stabilization may depend on the intermolecular interactions with arginine. In this section, we aim to provide an overview of the water replacement and glass dynamic hypothesis. In addition, we will elaborate on details of the existing experimental evidence of these two dominant theories. Moreover, a few factors that impact protein stability in the dry state will also be discussed.