Various pharmaceutical particles have been used in developing different drug delivery systems ranging from traditional tablets to state-of-the-art nanoparticle formulations. Nanoparticle formulations are unique in that the small size with huge surface area sometimes provides unique properties that larger particles and bulk materials do not have. Nanoparticle formulations have been used in improving the bioavailability of various drugs, in particular, poorly soluble drugs. Nanoparticle drug delivery systems have found their unique applications in targeted drug delivery to tumors. While nanoparticle formulations have been successful in small animal xenograft models, their translation to clinical applications has been very rare. Developing nanoparticle systems designed for targeted drug delivery. e.g., treating tumors in humans, requires clear understanding of the uniqueness of nanoparticles, as well as limitations and causes of failures in clinical applications. It also requires designing novel smart nanoparticle delivery systems that can increase the drug bioavailability and at the same time reduce the drug's side effects. (C) 2014 Elsevier Ltd. All rights reserved.