Cancer is a genetic disease caused by somatic mutation(s) in essential genes that regulate cell growth or survival. Advances in genetics have identified molecular defects that can be targeted by novel pharmaceutics that exploit the altered genetic machinery of tumor cells. Gene transfer also can be used to potentiate the host immune response to weak tumor antigens that may arise during the process of neoplastic transformation. Advances in our understanding of the mechanics of immune activation have led to development of immune-based strategies for gene therapy of cancer. Preliminary findings in a phase I trial of one such approach in patients with chronic lymphocytic leukemia (CLL) are encouraging. Conceivably, we soon may see the advent of effective gene therapy for patients with indolent B-cell malignancies.