Antineoplastic drugs play an important role in cancer therapy.  A growing number of patients and new fields of application have resulted in an increasing use of these agents.  Most antineoplastic drugs are classified as carcinogenic, mutagenic, or teratogenic for humans.  Antineoplastic drugs also cause adverse effects in health care workers who handle them.  In the late 1960s, acute symptoms by exposure to antineoplastic drugs were first reported.  In 1979, Falck reported a small increase in urine mutagenicity of nurse who handled antineoplastic drugs.  Thereafter several studies showed that association of occupational exposure to antineoplastic drugs with health effects such as DNA damage, chromosomal abnormalities, adverse reproductive outcomes, possibly leukemia and other cancers.  To prevent them, many guidelines for safe handling were published in various countries in 1980s, they are revised periodically afterward.  In 1990s, despite recommended safe handling procedures, environmental contamination with antineoplastic drugs was still observed in hospital and health care workers were still exposed.  In 2004, the National Institute for Occupational Safety and Health (NIOSH) published an Alert on hazardous drugs used in health care settings.  One recommendation was to consider the use of closed system drug transfer devices (CSTD) in addition to ventilated cabinets.  The effectiveness of CSTDs in reduction of environmental contamination and exposure of health care workers has been reported.  Here this report briefly reviews the history of the health effects of exposure to antineoplastic drugs and of safe handling.