It was discovered in the mid-1950s by Magee and Barnes that N-nitrosodimethylamine (NDMA) was hepatotoxic. The carcinogenicity of this compound and many other nitrosamines has since been tested by Magee, Druckrey, Preussmann, Schmahl, and others; the results of these pioneer works were summarized in two comprehensive reviews (1,2). The biochemical mechanisms of the carcinogenicity and the structure-activity relationship of the nitrosamines have since been studied by many investigators and the results have been summarized in three recent symposia (3–5). In this chapter, we will discuss the occurrence and carcinogenicity of nitrosamines, the enzyme mechanisms and the organ site of the activation, and the dose-response relationship in carcinogenesis.