Recent advances in molecular biology have fostered remarkable insights into the molecular basis of neoplasms. This new understanding of cancer pathogenesis suggests that restoration of the function of critical gene products could halt or reverse these mechanisms, thus having a therapeutic effect in cancer. The tumor suppressor p53 gene has been implicated in many inherited and sporadic forms of malignancy in humans. A number of preclinical experiments have demonstrated that restoration of the wild-type p53 function in the cancer cell by gene transfer is sufficient to cause antitumor effects such as cell-cycle arrest and induction of apoptosis. This approach has entered initial clinical testing and provided intriguing information about the intratumoral administration of an adenovirus vector expressing the wild-type p53 gene in non-small cell lung cancer patients.