Over the last decade, concerns about the hazards of handling cytotoxic chemotherapeutic agents increased as various studies were published. Analysis of these data suggest possible carcinogenic, teratogenic, and mutagenic risk for health professionals (predominantly nurses and pharmacists) that handle these drugs. However, the research is inconclusive. The nature of the problem, along with methodologic issues, may make it difficult or impossible to provide definitive data on the type and degree of risk for those exposed to chemotherapeutic agents. Guidelines and recommendations have been published by various groups including the Occupational Safety and Health Administration, the American Society of Hospital Pharmacists, the Oncology Nursing Society, and others. In essence, they recommend that only health professionals with specialized training should prepare or administer chemotherapeutic agents. In addition, equipment, unused drugs, and human excreta should be treated as chemically hazardous waste and disposed of according to the individual facility's policies and procedures. These guidelines should provide protection for those involved in preparing chemotherapy for administration, regardless of where this is done. Studies have shown differences in the degree and type of procedures followed and between existing procedures and actual practice. Some of these differences are based on the site of care (e.g., hospital [also influenced by bed size], private practice, or home care). Issues involved in implementing reasonable approaches to lower the relative risk for health-care professionals that handle cytotoxic chemotherapy will be discussed.