The delineation of the molecular basis of neoplasia provides the possibility of specific intervention by gene therapy through the introduction of genetic material for therapeutic purposes. In this regard, several gene therapy approaches have been developed for the treatment of cancer: mutation compensation, genetic immunopotentiation, molecular chemotherapy, inhibition of angiogenesis, replicative vector oncolysis, and chemosensitization or radiosensitization. Clinical trials have been initiated to evaluate safety, toxicity, and efficacy of each of these approaches, based on promising preclinical results. Various limitations that have been identified include lack of in vivo selective tumor delivery of vectors, minimal expression of therapeutic genes, immune response against vectors, and normal tissue toxicity. Combined modality therapy with gene therapy and chemotherapy or radiation therapy has shown promising results. It is expected that as new therapeutic targets and approaches are identified, combined with advances in vector design, that gene therapy will play an increasing role in clinical cancer treatment.