Nanostructures self-assembled from amphiphilic functional copolymers have emerged as safe and efficient nanocarriers for delivery of anticancer therapeutics. The development of this class of nanostructures has advanced from basic spherical micelles for delivery of small molecular hydrophobic drugs to a more complex functional structure for more efficient delivery of a wide range of therapeutics including small molecular drugs, macromolecular proteins and genes. This review describes physiological barriers for delivery of therapeutics, summarizes various approaches to overcome these barriers, and discusses the challenges in the current approaches for cancer therapy and perspectives for future solutions. (C) 2009 Elsevier Ltd. All rights reserved.