The physico-chemical properties of nanoparticles, as characterized under idealized laboratory conditions, have been suggested to differ significantly when studied under complex physiological environments. A major reason for this variation has been the adsorption of biomolecules (mainly proteins) on the nanoparticle surface, constituting the so-called "biomolecular corona". The formation of biomolecular corona on the nanoparticle surface has been reported to influence various nanoparticle properties viz. cellular targeting, cellular interaction, in vivo clearance, toxicity, etc. Understanding the interaction of nanoparticles with proteins upon administration in vivo thus becomes important for the development of effective nanotechnology-based platforms for biomedical applications. In this chapter, we describe the formation of protein corona on nanoparticles and the differences arising in its composition due to variations in nanoparticle properties. Also discussed is the influence of protein corona on various nanoparticle activities.