Development of gene therapy technologies is approaching clinical realization for the treatment of neoplastic diseases. The use of tumor suppressor genes has been one useful strategy in gene therapy. Modifications and development of vectors as well as increased knowledge of the anti-tumor mechanisms of the p53 will play a significant role in the further advancement of this therapy. Currently, several laboratories have demonstrated that intratumoral injection of a virus carrying the p53 gene decreases tumor size in pre-clinical and clinical studies. Our lab has focused on a tumor-bearing mouse model in which intravenous delivery of liposome: p53 complexes decreases tumor growth. Although a high transfection efficiency of the tumor was thought to be necessary for gene therapy to exhibit anti-tumor activity with tumor suppressor genes, marked inhibition of the tumor occurs even with a low transfection efficiency. p53 may exhibit its bystander anti-tumor effect, at least in part, through an antiangiogenic effect. We believe that understanding the mechanism by which the p53 tumor suppressor gene inhibits tumor growth will lead to improvement in cancer therapy.