It has long been promised that dendritic cell immunotherapy would revolutionize the treatment of neoplastic disease. Now, more than 10 years since the publication of the first clinical data, a firmer understanding of immunology and dendritic cell biology is beginning to produce interesting clinical results. This article reviews the clinical trials that established many of the concepts with which today's investigators are achieving improved results, discusses issues in dendritic cell immunotherapy that are currently unresolved, and offers a perspective on the strategies that the authors believe will be important for the design of future vaccine trials, including the use of Toll-like receptor agonists as maturation agents, the accessory use of the plasmacytoid dendritic cell subset, and the maximization of T-cell help.