The development of vaccines to induce tumor-specific immunity in patients with cancer has as emerged as a major area of investigation. The identification of antigens uniquely expressed by tumor cells and a heightened understanding of tumor immunology have resulted in efforts to activate host immunity to recognize and reject tumor cells. Tumor-associated antigens and peptides, genes encoding tumor antigens, and modified whole tumor cells have been used in preclinical studies with provocative results. Potent antigen-presenting cells, known as dendritic cells, have also been modified using peptides, genetic material, or whole tumor cells to present tumor antigens in the context of co-stimulation to overcome tolerance and induce tumor-specific cell killing. Promising data generated from the preclinical evaluation of cancer vaccines have resulted in the initiation of clinical trials to define the associated toxicity profile, immunologic response, and clinical impact of this treatment approach. We summarize the preclinical and clinical experience in this expanding area of investigation. Cancer vaccines hold much promise; however, many unresolved questions remain in the effort to generate a clinically meaningful treatment strategy.