This review provides a review of the basic biology of the major cytokines under consideration for use in tumor immunotherapy. The authors also describe the clinical role of cytokine therapy for human tumors, with a focus on melanoma and renal cell carcinoma. Finally, they present details of new cytokines and suggest possible direction for future clinical investigation using new cytokines or combinations of biologic agents. A better understanding of cytokine biology, coupled with new insights into the role of immunoregulation and the microenvironment in patients who have cancer, has provided new therapeutic targets for the treatment of human cancer.