Background: Nanoparticulate delivery systems receive a lot of attention in pharmaceutical research and market due to their in vivo stability, ability to protect entrapped drug, and ease of cellular penetration. The hemo-compatibility and the clearance half-life are important parameters of the nanodelivery systems that will be administered through intravenous route. Natural components, like blood plasma proteins are ideal sources of biomaterial for such systems with their long in vivo half-lives. Methods: The aim of this work is to review in vitro, in vivo and clinical findings of nanocarriers based on blood plasma proteins, namely albumin, lipoproteins, fibrin/fibrinogen, transferrin. Plasma protein based nanocarriers loaded with different bioactive molecules (i.e., anti-cancer, antiviral, anti-epileptic drugs, DNA) have been developed using different preparation methods like desolvation, emulsification, nab-technology, complexation methods. Results: Human serum albumin has attracted the most attention in the last decade as nano-carrier due to its biocompatibility, high binding capacity to various drugs, and easy derivatization by covalent methods. Commercial products of albumin nanoparticles have emerged on the market after its recognition. Low and high density lipoproteins have recently been considered as valuable natural material for preparing hemocompatible small (app 20 nm) lipid-protein vesicles. For other proteins of plasma, however, there are a limited number of studies that explored their potential as nanocarrier formulation. Therefore, there is huge research potential for investigating the proteins like globulins, fibrinogen and transferrin as part of nanocarrier core. Conclusion: Plasma protein based nanoparticulate delivery systems, especially albumin based ones have opened up and also will continue to open new treatment strategy options for treating cancer, AIDS and other complex life threatening diseases with advances in nanotechnology and science.