Immunotherapy with vaccines represents a novel, targeted nontoxic modality for the therapy of prostate cancer. Systemic immune responses to candidate prostate cancer antigens have been induced in a tumor that has been conventionally viewed as refractory to immunotherapy. Autologous dendritic cell vaccines expressing prostate-specific antigens have shown promising clinical outcomes in a randomized trial in metastatic androgen independent prostate cancer. Other vaccine approaches include granulocyte-macrophage colony-stimulating factor modified tumor cell vaccines and poxvirus vaccines. A combination of vaccines with chemotherapy, radiotherapy, and other biologic agents is also being evaluated. Efforts to optimize vaccine approaches and select ideal patient populations need to continue because there is no evidence supporting a single superior approach.