Interferons, a group of cytokines with antiangiogenic, direct antitumour and immunostimulating properties, have shown significant activity against osteosarcoma in vitro and in xenograft models. They have also been used in osteosarcoma clinical trials as a single adjuvant to surgery, with an apparent increase in relapse-free survival. In the ongoing EURAMOS 1 clinical trial, interferon α-2b is evaluated as an adjuvant treatment in osteosarcoma. This article reviews the rationale for the use of interferon in cancer with special reference to the treatment of osteosarcoma, including all published data of clinical efficacy in this disease. Pediatr Blood Cancer 2010;54:350–354. © 2009 Wiley-Liss, Inc.