Résumé : Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine involved in systemic, autoimmune, and inflammatory diseases, such as obesity, rheumatoid arthritis, and systemic lupus erythematosus. For the 2 past decades, MIF has been reported to participate in carcinogenesis, disease prognosis, tumor cell proliferation, invasion, and tumor-induced angiogenesis in many cancers. The purpose of this article is to review published experimental and clinical data for MIF and its involvement in upper aerodigestive tract cancers. Based on the current literature, we propose a biomolecular model describing the mechanisms underlying the involvement of MIF in the initiation, progression, apoptosis, and proliferation of head and neck tumor cells. In reference to this model, potential therapeutic approaches based on the use of MIF antagonists and neutralizing antibodies are described. It is concluded that MIF is a promising target for future therapeutic strategies, both with and without chemoradiation strategies.