Since the discovery of nitric oxide and nitrogen oxides as endogenous mediator of different physiological and pathophysiological mechanisms, there has been this dichotomy as to where NO is toxic or beneficial. Even the initial discovery of NO and related nitrogen oxides in cancer, both positive and negative effects were described. Since these discoveries over 20 years ago, this area of biomedical research has exploded. However, we are now just starting to understand the how the chemistry and the timing of specific reaction influences the biology. Examination of different signal transduction mechanisms, biochemical modification and toxicological responses with respect to concentration and redox environment can provide a quantitative picture where NO and nitrogen oxides can have pro and anti carcinogenic effects.