A human health hazard may constitute a variety of hazards that are encountered in an animal facility. Health hazards include physical, chemical, radioactive, or biological hazards such as cage and rack washers, chemicals used for cleaning and disinfection, experimental drugs or biologics, radioactive isotopes, zoonotic diseases, allergens, experimental infectious agents, or biological toxins. This article will focus on experimental infectious agents and biological toxins (biohazards) that are hazardous to both animals and humans and require biological containment (biocontainment) to prevent their inadvertent release into the environment. Key areas for safely managing a biocontainment animal care and use program and vivarium are described. While scientific research involving health hazards has created some challenges, it has also provided some excellent advances in methods and technologies. The ideas and approaches in this article will be useful for those just entering this field of research and those who have committed their careers to the safe use of animals exposed to biohazards.