Long-term stability is critical in the successful development of pharmaceuticals, including macromolecular ones, such as proteins. Due to the relative instability of aqueous solutions of proteins, they are typically stored in a freeze-dried (lyophilized) state. However, proteins reversibly (and sometimes even irreversibly) denature upon lyophilization and consequently adopt conformations markedly distinct from the native ones. This phenomenon may profoundly affect deleterious processes in lyophilized proteins, e.g. moisture-induced aggregation, as illustrated in this review with bovine serum and recombinant human albumins.