The term hazardous drug (HD) includes medications that have any of the following properties: carcinogenicity, teratogenicity, reproductive toxicities, genotoxicities, toxicities at low doses, and a structure that mimics other drugs meeting the criteria. Numerous studies continue to demonstrate widespread environmental contamination and human uptake of these agents. Safe handling guidelines have existed for more than 30 years but have not been routinely implemented. USP General Chapter 800 (USP <800>) represents a new enforceable standard for HD safety. Nurses will need to understand the impact of USP <800>, which is expected to be enforced beginning December 1, 2019.