Interleukin‐6 (IL‐6) plays a major role in the response to injury or infection and is involved in the immune response, inflammation, and hematopoiesis. Its deregulation impacts numerous disease states, including many types of cancer. Consequently, modulating IL‐6 may be an innovative therapeutic strategy in several diseases. A review of relevant published literature regarding IL‐6 and its receptor was performed. In addition, a review of the relevance of this cytokine system to human illness, particularly in cancer, was undertaken. IL‐6 is a pleiotropic cytokine that is involved in the physiology of virtually every organ system. Aberrant expression of this cytokine has been implicated in diverse human illnesses, most notably inflammatory and autoimmune disorders, coronary artery and neurologic disease, gestational problems, and neoplasms. In cancer, high levels of circulating IL‐6 are observed in almost every type of tumor studied and predict a poor outcome. Furthermore, elevated IL‐6 levels are associated strongly with several of the striking phenotypic features of cancer. Several molecules have been developed recently that target the biologic function of IL‐6. Early results in the clinic suggest that this strategy may have a significant salutary impact on diverse tumors. The field of cytokine research has yielded a deep understanding of the fundamental role of IL‐6 and its receptor in health and disease. Therapeutic targeting of IL‐6 and its receptor in cancer has strong biologic rationale, and there is preliminary evidence suggesting that targeting of the IL‐6 system may be beneficial in the treatment of cancer. Cancer 2007. © 2007 American Cancer Society.