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Healthcare workers are exposed to numerous hazardous drugs including antineoplastic agents, antiviral drugs, hormones, and bioengineered/miscellaneous drugs. The National Institute for Occupational Safety and Health (NIOSH) in the U.S. has defined hazardous drugs as those that exhibit one or more of the following characteristics in animals or humans: carcinogenicity, teratogenicity, reproductive toxicity, organ toxicity at low does, genotoxicity, and toxic profiles of new drugs that mimic existing drugs. The actual risk to healthcare workers depends on drug toxicity, route of drug entry (e.g., inhalation, percutaneous, ingestion), and work practice handling and exposure and controls. Many of these drugs affect human cell systems through DNA damage, interference with cell growth, or may cause mutations. In considering the hazardous nature of the drug, NIOSH examines the dose for animal testing that results in reproductive or developmental toxic effects, any available human data with toxic effects, and those drugs requiring safe-handling practices as determined from the manufacturer. There are many drugs that are considered hazardous and all of these cannot be discussed here. However, examples will be provided as to effects of antineoplastic agents and non-antineoplastic agents. The issue of safety culture is always important in terms of prevention and control strategies and recognition of the harmful effects of these substances.