Tumor resistance to cytotoxic therapeutics coupled with dose-limiting toxicity is a serious hurdle in the field of medical oncology. In the face of this obstacle, nitric oxide has emerged as a powerful adjuvant for the hypersensitization of tumors to more traditional chemo- and radio-therapeutics. Furthermore, emerging evidence indicates that nitric oxide donors have the potential to function independently in the clinical management of cancer. Herein, we discuss the role of nitric oxide in cancer and the potential for nitric oxide donors to support conventional therapeutics. (C) 2013 Elsevier Inc. All rights reserved.