Many antineoplastic agents have been shown to be mutagenic, teratogenic and carcinogenic in experimental studies and secondary malignant neoplasms are known to be associated with several specific therapeutic treatments. However, the occupational exposure to antineoplastic drugs in health care workers has different routes of exposure, dose and duration compared to patients undergoing treatment protocols. The aims of this review are to analyze and to update the National and International Classification, and deepening the topics of occupational exposure, current operating conditions, the technical and operational progress to reducing the exposure, the epidemiological evidence and exposure measurement data available. Finally, we illustrate the dispersion in the environment as a real risk for the general population.