Cytokines are endogenous small peptides that regulate cell growth and proliferation. In allogeneic transplantation, they function as critical immunologic mediators. Allograft rejection is dependent on interactions between antigen-presenting cells, T lymphocytes, accessory molecules, and proinflammatory cytokines (interleukins-1, -2, and -6; interferon-gamma; and tumor necrosis factors). Alternatively, other cytokines (interleukins-4, -5, and -10; transforming growth factor-beta) may suppress allograft rejection. Observation and manipulation of cytokine responses are an essential component of the immunopharmacology and clinical management of transplant recipients. Specific areas of interest include immunologic monitoring, pharmacologic immunosuppression, monoclonal antibody development, induction of tolerance, and the OKT3-related cytokine release syndrome. This review explores the impact of advances in cytokine physiology and biotechnology on clinical transplantation.