Tumor antigen genetically modified dendritic cells (DC) have been extensively tested as cancer vaccine approaches in preclinical models. This testing has provided evidence of their ability to generate coordinated antitumor CD8+ cytotoxic T lymphocyte (CTL) and CD4+ T-helper cell responses. Their antitumor activity compared favorably to multiple other vaccination strategies in mice. This approach has been brought to patients within nine pilot clinical trials reported to date. These clinical trials have tested both RNA and DNA as means to introduce the foreign genetic material into the DC. Administration to human subjects has proven to be both feasible and safe. There is clear evidence of the ability to activate both CD8+ CTL and CD4+ T-helper cells, which has been the major scientific endpoint in most of these trials. However, antitumor activity has been marginal thus far. In conclusion, tumor antigen genetically modified DC are a feasible strategy to activate tumor-specific T cells in humans.