Recent advances in understanding tumor-specific immunity have introduced new excitement in the clinical development of vaccines for the treatment of cancer. A better understanding of basic immunologic principles has led to a variety of techniques for enhancing tumor-specific immunity through vaccination. Approaches to antigen-specific immunotherapy have included: (1) peptides, usually in combination with various immunological adjuvants; (2) soluble proteins; (3) dendritic cells pulsed with specific antigens; (4) monoclonal antibodies; (5) recombinant plasmid DNA; (6) autologous and allogeneic tumor cells; and (7) recombinant viral vectors. This review will focus on the use of viral vectors, which offer unique advantages as both gene delivery vectors and as agents supplying additional adjuvant activity for vaccination. Viral vectors are particularly attractive for immunotherapy since they mimic natural infection and can induce potent immune responses. Replicating and nonreplicating members of the poxvirus family have been widely studied for expression of tumor antigens and other immunomodulatory genes, such as cytokines and costimulatory molecules. Although a large number of TAAs are available for insertion into viral vectors, this review will discuss the preclinical and clinical development of prostate-specific antigen (PSA) and carcinoembryonic antigen (CEA) poxviral vaccines, as models of the pox viral vaccine approach.