Despite the still poorly understood complexity of tumor-host immune interactions, the use of cellular vaccines (particularly dendritic cells) has made it possible to reliably generate tumor antigen-specific T cells, both in animal models and in humans. These encouraging pre-clinical results have led to a translation of these immunotherapeutic strategies into clinical trials. With numerous trials still underway, their general outcome has so far been disappointing, and the discrepancy between pre-clinical data and clinical response rates is striking. Thus, either the pre-clinical models have not been representative of the human situation or the translation into human clinical trials is still sub-optimal. Here we suggest new avenues of clinical research to further improve cellular cancer immunotherapy.