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The cytokine network is a complex and dynamic system, involved in numerous biological responses in the human body. This review of the current literature describes the role of cytokines and their interaction with the coagulation system, specifically in the maintenance of the thrombo-hemorrhagic balance in vivo in human subjects and in animals. In general, cytokines are thrombogenic, but they are amenable to therapeutic manipulations and hence are a potentially attractive tool in the clinician's armamentarium. Studies of the effects of cytokines in vivo are difficult because cytokines act in a very finite microenvironment and, although their actions are significant, they are transient. Most of the available clinical data related to interactions between cytokines and the coagulation system focuses on the role of tumor necrosis factor-alpha and interleukin-1 in septicemia and septic shock. However, several other cytokines and related proteins, such as platelet activating factor and plasminogen activator inhibitor, are also known to influence coagulation and thrombosis. These factors interact closely with cytokines, and have been included in this review for a better understanding of their interactions with traditional cytokines. Studies that utilize cell culture systems do not accurately model the in vivo status of this complex system and, hence, this review has excluded such studies. The role of the cytokine network in coronary artery disease, angiogenesis, or neoplasia has been addressed elsewhere by other workers and is not discussed here. By emphasizing important in vivo interactions, the intention of this review is to serve as an impetus to further translational research, both clinical and in the laboratory.