Oral delivery of drugs to the small intestine is an important topic in the research and development of more effective oral dose forms. This review highlights several important developments in this area. An overriding theme in drug delivery to the small intestine is how to increase the efficiency (ie, how to increase bioavailability) of absorption. The role of P-glycoprotein and intestinal transporters is discussed in this regard. These systems are normally studied under defined in vitro conditions; recent data suggest that this approach, though useful, may not fully represent the in vivo situation. Recent advances and issues in the characterization and prediction of drug absorption from the small intestine are reviewed. These efforts, if successful, will shorten development timelines by eliminating compounds with poor absorption characteristics early in the process. Nanoparticulate delivery systems and those prepared by microfabrication technology are being used to improve bioavailability of poorly absorbed drugs. A relatively new technique (electroporation) has been proposed to enhance oral delivery of macromolecules, still an unrealized objective in drug delivery.