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Synthetic gene delivery vehicles have made significant progress in the past decade in demonstrating strong potential for targeted delivery to specific cells, low toxicity and immunogenicity and large carrying capacity. However, significant advances must still be made to increase the efficiency of both polymer and lipid vehicles. Furthermore, techniques to generate more effective targeting moieties for a variety of cell types, as well as means to consistently assemble vectors containing these targeting ligands, are areas for further improvement. This review focuses on significant recent advances in generating a number of novel targeted vectors, and discusses progress in the development of new genetic and chemical systems to enhance the targeting, assembly and biocompatibility of synthetic vectors.