Nanomedicine applications have recently gathered great attention in terms of their revolutionary properties and multivalency. Nanoparticles (NPs) have proven useful owing to their size, surface and kinetics advantages, as well as their ability to be functionalized with targeting, imaging and therapeutic moieties. Nuclear medicine is actively involved in nano-research innovative breakthrough efforts in multiple applications, through the radiolabeling of NP structures. There are several ways that NP-radiolabeling can be approached depending on the radionuclide that is used and the NP type. The radiolabeling of NPs with the most widely and easily available radiometal, which is 99mTc, is the focus of this review. Copyright © 2013 John Wiley & Sons, Ltd.