Over the past decade, the unprecedented growth in science and technology has fueled the development of novel treatment strategies to combat disease. The creative and innovative efforts of scientists and clinicians to overcome the multitude of unforeseen obstacles to success is no better exemplified than in the field of cancer gene therapy. Since its inception, developers of cancer gene therapy have been charged with the challenge of altering basic tumor biology or, alternatively, the host responses for the purpose of tumor eradication and prevention. Several major therapeutic strategies have emerged from preclinical studies, and results from these early studies hold promise for altering the clinical outcome in a variety of malignancies. These strategies may be broadly subcategorized and range in intent from alteration of the tumor cell phenotype by replacement of defective cellular response genes (e.g., mutated or deleted tumor suppressor genes) to the enhancement of the immunological response to cancer (e.g., amplification of the cell surface antigen signature or modulation of the host response). Not surprisingly, the increasingly intricate nature of tumor biology revealed over the past several years has effectively raised the bar of success for those involved in the development of effective molecular and cancer gene therapy strategies. This, in turn, has led to the development of more complex therapies that frequently draw upon multiple disciplines in an effort to optimize treatment response.