Nitric oxide (NO) is a key molecule involved in many physiological functions. However, evidence is accumulating that sustained high levels of NO over extended periods of time contribute to carcinogenesis. This article reviews recent data and outlines a dual role of NO in animal carcinogenesis. Following an inhibition of NO production, some studies find a protection, while others find an exacerbation of tumorigenesis. These studies reflect the importance of (i). choosing the appropriate compound for NO inhibition; and (ii). genetic background, target tissue, levels of NO, and surrounding free radicals in the overall affects of NO on the tumor growth. These findings highlight the importance of further study of the use of NO inhibitors to inhibit human carcinogenesis.