Abstract After briefly introducing the theoretical equations for DLS based particle size analysis, the need for angular dependent DLS investigations is emphasized to obtain correct particle sizes. Practical examples are given that demonstrate the possible magnitudes of errors in particle size if DLS is measured at one large scattering angle, only, as done by essentially all, most frequently utilized commercial “single angle” particle sizers. The second part is focused on a novel DLS application to sensitively trace (nano)particle interactions with concentrated blood serum or plasma that leads to the formation of large aggregates in a size regime of ≫100 nm. Most likely, such aggregates originate from protein induced bridging of nanoparticles, since it is well known that serum proteins adsorb onto the surface of essentially all nanoparticles utilized in medical applications. Thus, the protein corona around nanoparticles does not only change their biological identity but to a large extend also their size, thus possibly affecting biodistribution and in vivo circulation time.