Nanoscale objects lose their original identity once in contact with biological fluids and get a new biological identity, referred to as a protein corona (PC). The PC modifies many of the physicochemical properties of nanoparticles (NPs), including surface charge, size, and aggregation state. These changes, in turn, affect the biological fate of NPs, including their biodistribution, pharmacokinetics, and therapeutic efficacy. It is well known that even small differences in the composition of a protein source (e.g., plasma and serum) can considerably change the composition of the corona formed on the surface of the same NPs. Recently, it has been shown that the PC is intensely affected by the patient's specific disease. Consequently, the same nanomaterial incubated with proteins of biological fluids belonging to patients with different pathologies adsorbs protein coronas with different compositions, giving rise to the concept of the personalized protein corona (PPC). Herein, we review recent advances on the topic of PPC, with a particular focus on their clinical significance.