Cancer immunotherapy seeks to mobilize a patient's immune system for therapeutic benefit. It can be passive, that is, transfer of immune effector cells (T cells) or proteins (antibodies), or active, that is, vaccination. Early clinical trials testing vaccination with ex vivo generated dendritic cells (DCs) pulsed with tumor antigens provide a proof-of-principle that therapeutic immunity can be elicited. Yet, the clinical benefit measured by regression of established tumors in patients with stage IV cancer has been observed in a fraction of patients only. The next generation of DC vaccines is expected to generate large numbers of high avidity effector CD8 T cells and to overcome regulatory T cells and suppressive environment established by tumors, a major obstacle in metastatic disease. Therapeutic vaccination protocols will combine improved DC vaccines with chemotherapy to exploit immunogenic chemotherapy regimens. We foresee adjuvant vaccination in patients with resected tumors but at high risk of relapse to be based on in vivo targeting of DCs with fusion proteins containing anti-DCs antibodies, antigens from tumor stem/propagating cells, and DC activators.