The delivery of cell-based vaccines that exploit natural mechanisms of antigen presentation represents a promising approach for immunotherapy of cancer. This strategy tests the hypothesis that ex vivo manipulation and reinjection of cellular products can induce immune responses and circumvent immune incompetence to achieve clinically significant results. Whole or modified tumor cell vaccines and antigen-loaded dendritic cells (DC) are under intense clinical and scientific evaluation, but other cell-based approaches including the use of activated B lymphocytes have shown promise in preclinical in vitro models. RNA-transfected CD40-activated B cells may fill a particular need in pediatric cancer patients and other patients in whom DC manufacturing is problematic. Thus far, evidence of immunological activity of cell-based vaccines has surpassed that of clinical efficacy, but recent advances and strong safety data from multiple approaches justifies randomized studies in healthier patients who are more likely to benefit.