Nanoparticles are used widely in our lives, but the understanding of their impacts on human and environmental health is still limited, at least due in part to the fact that nanoparticles are mixtures. This review describes that "nanotoxicity" is actually a test of the overall effect of a nanoparticle mixture: starting materials for nanoparticle preparation, surface coating agents, surface reaction-generated species, and transformed byproducts of the nanoparticle in biological and environmental media, as well as variations of the intrinsic nanoparticle structures.