This article describes sources of workplace contamination with hazardous drugs and how healthcare workers may be exposed to hazardous drugs during the course of their duties. For a description of some of the hazards associated with working with antineoplastic drugs in the pharmacy and discussion of some of the published recommendations for their safe handling, see the article by Roussel and Connor in the May 2013 issue of The Oncology Pharmacist. Measurement of surface contamination is currently the only indication of the amount of environmental contamination in areas where hazardous drugs are prepared, administered to patients, or otherwise handled (such as receiving areas, in transit throughout the facility, and waste storage areas). Although limited associations have been demonstrated between surface contamination and actual worker exposure, surface contamination is the most commonly used metric for evaluation of the workplace for hazardous drugs. Workplace contamination with hazardous drugs in the United States and other countries has remained fairly constant over the past decade or more, indicating that worker exposure probably has not changed considerably over that time, despite efforts to reduce or eliminate environmental contamination. The introduction of Class II biological safety cabinets (BSCs) for the preparation of hazardous drugs in the 1980s substantially reduced the potential for worker exposure, but BSCs did not prove to be as efficient at reducing contamination as first believed. The recent use of isolators has not been widespread in the United States, nor have they proven to offer more protection to workers than do BSCs, as contamination from the inside surfaces of the isolator may be transferred to the outside of syringes and infusion bags. Use of robotic systems to prepare hazardous drugs may reduce environmental contamination and worker exposure to these drugs; however, their high cost makes them prohibitive for all but large cancer centers. The addition of closed system drug transfer devices (CSTDs) for the preparation and administration of hazardous drugs has been shown to reduce surface contamination and possibly worker exposure, but they do not totally eliminate it.