Magnetic nanoparticles have attracted attention in nanomedicine owing to their potentialities offered in bioimaging, drug release, magnetic hyperthermia and diagnosis devices. The conjugation of selected affinity ligands on their surface enables the specific targeting of overexpressed receptors in diseased tissues or cells and can increase for instance the therapeutic index of drugs used in chemotherapy or the diagnosis value of images in magnetic resonance imaging. The bioconjugation appears as the ultimate step in the design of targeted magnetic nanoparticles (MNPs) and is therefore critical since it can determinate their final in vivo biodistribution. This chapter summarizes the main bioconjugation procedures, followed by the description of the interface between MNP and the biological environment. In the last part, the critical parameters affecting the targeting efficiency and the MNP biodistribution are presented, as well as preassessment methods