Successful development of marketable freeze-dried protein formulations requires adequate stabilization of the active biopharmaceutical ingredient. The choice of a stabilizer must therefore be based on sound knowledge of the physical and chemical properties of the excipients and specific needs of the protein component. Amino acids, such as arginine, have exhibit cryo- and lyoprotective effects similar to those of sugars and/or polymers and may therefore be considered to be an alternative approach to these established formulation strategies. The chemical structure and physicochemical characteristics of arginine are unique among amino acids and can provide additional benefits to freeze-dried protein formulations with regard to liquid and solid state stability. This mini-review provides a brief summary of research focused on the application of arginine in freeze-dried protein pharmaceuticals, including a discussion of its basic physical and chemical attributes as well as thermal behavior in the frozen and solid states. Mechanisms contributing to solid-state stabilization by arginine are discussed in the context of available stability studies on arginine-containing protein formulations. This mini-review seeks to deepen the understanding of the opportunities and challenges associated with arginine-based preparations for freeze-dried protein pharmaceuticals.