Tumor targeting is a crucial factor in the success of cancer gene therapy, especially in cases involving advanced cancers. Given that therapeutic cytocydal transgenes are delivered in vivo, various tumor-targeting strategies are currently being investigated. Among them, a promising approach is to exploit receptor-mediated cell entry in designing viral or nonviral vectors that are directed preferentially to cancer tissues, the ligands of these vectors being specific to certain cancer tissues. This review focuses on integrins, transferring receptors, and folate receptors that have been extensively studied in ligand –directed tumor targeting. Pathohysiological and pharmacological aspects of these ligand/receptor interactions and their applications for ligand-directed vectors in cancer gene therapy will be reviewed.