The management of metastatic renal cell carcinoma (mRCC) remains a therapeutic challenge; less than 10% of patients survive for longer than 5 years. The resistance of renal cancer to chemotherapy may be explained by high levels of the multidrug resistance gene, MDR1. Immune-based treatments for renal cancer have been explored because of their unusual susceptibility to immunological assault. However, response rates to cytokines such as interleukin-2 and interferon-alpha have ranged from only 10% to 20%, prompting other immunotherapy approaches, such as allogeneic stem-cell transplantation, to be investigated. Several clinical trials have provided evidence of partial or complete disease regression in refractory mRCC following nonmyeloablative stem-cell transplantation. This effect is because of a donor antimalignancy effect mediated by immunocompetent donor T cells, called graft-versus-tumor effect. Unfortunately, less than 30% of patients who could have this procedure will have a human-leukocyte-antigen-compatible sibling, and attention is focusing on alternative donors such as matched unrelated donors and partially mismatched related donors. Despite the improved safety of nonmyeloablative conditioning regimens, transplant-related toxic effects (particularly graft-versus-host disease) remain obstacles to the safe and effective use of this treatment. Regardless of these limitations, innovative approaches have attempted to harness the potential of the graft-versus-tumor effect in mRCC and other solid tumors.