Nanoparticles exposed to biological fluids such as blood, quickly interact with their surrounding milieu resulting in a biological coating that results in large part as a function of the physicochemical properties of the nanomaterial. The large nanoparticle surface area-to-volume ratio further augments binding of biological molecules and the resulting biomolecular or protein corona, once thought of as problematic biofouling, is now viewed as a rich source of biological information that can guide the development of nanomedicines. This review gives an overview of the utility of the protein corona in proteomic profiling and discusses how a better understanding of nano-bio interactions can accelerate the clinical translation of nanomedicines and facilitate the identification of disease-specific biomarkers. With the FDA requirement of the protein corona analysis of nanoparticles in place, it is envisaged that analyzing the protein corona of nanoparticles on a case-by-case basis can provide highly valuable nano-bio interface information that can aid and improve their clinical translation.