Bioreducible polymers, which possess mainly disulfide linkages in the polymer structures, have appeared as ideal gene delivery carriers due to the high stability in extracellular physiological condition and bioreduction-triggered release of genetic materials, as well as decreased cytotoxicity because intracellular cytosol is a reducing environment containing high level of reducing molecules such as glutathione. This review will describe the initiation and recent advances in the development of bioreducible polymers for gene delivery, which includes reducibly cross-linked PEIs, polypeptides, polyion complex micelles, and poly(amido amine)s. There have been extensive researches performed to exhibit great gene delivery efficacy but still several important issues about pharmacokinetics or safety should be answered thoroughly for further rational design of bioreducible polymers having potentials in human gene delivery systems. (C) 2010 Elsevier Ltd. All rights reserved.