In agricultural commodities, the occurrence of deoxynivalenol (DON) has been reported all over the world, with levels varying among grain types and years of production. The grain supply chain, including growers, buyers, and end users, have effectively managed DON with strategies to control this issue systematically. The safety of consumers is ensured through use of these management strategies. This is observed in this review of the North American systems. This article describes the occurrence and management of DON in North America, which is accomplished by 1) a review of the toxicological effects of DON; 2) a review of publically available data and introduction of new information regarding the occurrence of DON in wheat, maize, and barley in North America, including variability due to growing regions, grain varieties, and year of production; 3) an overview of industry practices to reduce DON contamination from field through milling when necessary; 4) a review of how all in the value chain, including growers, buyers, and end users, have effectively managed DON for more than 20 years; 5) a description of current maximum limits associated with DON; and 6) the economic impact of any potential changes in international regulations.