Cancer vaccines are examples of active immunotherapy. In pediatric malignancy such active strategies may be particularly problematic because of immune suppression produced by the tumor or its intensive treatment with combined chemotherapy. Nonetheless, the expression of tumor-specific and tumor-associated antigens on a range of pediatric tumors has encouraged investigation of the approach in patients with either bulky or minimal residual disease. Here we describe promising results in neuroblastoma and acute leukemia, suing genetically modified whole cell vaccines, peptides, and dendritic cells. The difficulties of conducting and evaluating such studies in a pediatric population are also described, and a strategy for cancer vaccine development is outlined.