The surface properties of nanoparticles (NPs) dictate their interaction with the outside world. The use of precisely designed molecular ligands to control NP surface properties provides an important toolkit for modulating their interaction with biological systems, facilitating their use in biomedicine. In this review we will discuss the application of the atom by-atom control provided by organic synthesis to the generation of engineered nanoparticles, with emphasis on how the functionalization of NPs with these "small" organic molecules (Mw < 1000) can be used to engineer NPs for a wide range of applications. (C) 2016 Elsevier Ltd. All rights reserved.