The toxicity of antineoplastic drugs in patients has been well-known since their introduction in the 1940s and 1950s. Because most antineoplastic medications have nonselective mechanisms of action, these agents affect noncancerous cells as well as cancerous cells, resulting in numerous adverse effects. When secondary cancers began to develop in patients treated with these drugs, concern was raised that healthcare workers also could be at risk for harmful effects from antineoplastic agents as a result of occupational exposure. In addition to the capability of many of the antineoplastic drugs of causing cancer, acute illnesses, and organ toxicity, evidence points to teratogenic and adverse reproductive outcomes in patients exposed to these agents. In current practice, antineoplastic medications are administered under controlled regimens that are designed to optimize benefits to patients while minimizing the risk for adverse effects. The safety of the patient is the primary focus. However, these procedures may result in job-related exposure of healthcare workers who are involved in patient treatment and related activities, such as storage, transportation, and disposal of the drugs. Awareness of the possible adverse health effects in workers during the 1980s prompted several organizations, including the Occupational Safety and Health Administration (OSHA), the Oncology Nursing Society (ONS), and the American Society of Hospital Pharmacists (ASHP, now the American Society of Health-System Pharmacists) to issue safe handling guidelines for antineoplastic drugs. Despite these improvements in guidance and recommendations, more recent studies have shown that workers continue to be exposed to these toxic agents. In 1995, OSHA updated its recommendations and included some non-antineoplastic medications in its list of hazardous drugs. The National Institute for Occupational Safety and Health (NIOSH) issued an alert in 2004 reviewing literature on hazardous drug exposure and recommending a program of safe drug handling. This alert incorporated a comprehensive list of hazardous drugs that require special handling by healthcare workers. Although most of the drugs are antineoplastic agents, approximately one third are used to treat other diseases. This list was updated and expanded in 2010 to include newly-approved drugs and existing drugs with new health warnings.