Gene therapy is one of the promising strategies in cancer treatment. Recent studies identified molecular targets on angiogenically activated endothelial cells that can be used to deliver gene-transfer vehicles to the tumor site specifically. Furthermore, non-viral vehicles are emerging as an alternative for traditional viral gene-therapy approaches. Here, we describe how viral and non-viral gene-transfer vehicles have been and can be modified to target tumor endothelial cells for anti-angiogenesis gene therapy. Improving the specificity and safety of existing gene-therapy vehicles will make angiogenesis-targeted cancer gene therapy a valuable tool in the clinical setting.