Background: Cytokines provide important intercellular signals in inflammation, immunity and tumor and endothelial cell biology. Several cytokines have therapeutic potential when delivered exogenously alone or in combinations with chemotherapy or other biological agents. Objectives: To summarize current data on the biology and therapeutic use of human cytokines in malignancy. Methods: The review focuses on the most important physiological and pathological functions of each cytokine and a unifying concept for its potential role in human malignancy based on preclinical models and current published literature. Results/conclusions: Interleukin-2 is the model cytokine for the study of other cytokines that have similar or distinct properties with potential for superior therapeutic uses. Ongoing studies of cytokine networks involved in normal and pathological processes, along with enhanced knowledge of mechanisms of counterregulation and resistance, will guide future therapeutic strategies.