In nanomedicine, the widespread concern of nanoparticles in general, and dendrimers, in particular, is the analysis of key in-vivo physicochemical parameters to ensure the preclinical and clinical development of 'safe' bioactive nanomaterials. It is clear that for biomedical applications, biocompatible dendrimers, used as nanocarriers or active per se, should be devoid of toxicity and immunogenicity, and have adequate PK/PD behaviors (adequate exposure) in order to diffuse in different tissues. Functionalization of dendrimers has a dramatic effect on in-vivo physicochemical parameters. In this review, we highlighted key in-vivo physicochemical properties, based on data from biochemical, cellular and animal models, to provide biocompatible dendrimers. Up-to-date, only scarce studies have been described on this topic.