The mechanisms for controlling microbial contamination in research animals are similar to those for preventing exposure among animal handlers to naturally occurring pathogens, research-related biohazards, or animal allergens. Research and resource preservation are the primary goals of each approach, and an appropriate assessment of risk is their foundation. The identification of potential risks enables the implementation of relevant risk management or control measures. This article summarizes the components of an occupational health and safety program for animal handlers, including screening, training, work practices, effective use of engineering controls, selection and use of personal protective equipment, and emergency response protocols. The features of a risk assessment and risk management program and the level of interaction and training required to implement and sustain the program correlate well with programs designed to control microbial contamination in laboratory animals. This article includes an explanation of the five Ps of risk assessment and risk management. Pathogens and the proposed experimental procedures account for the first two Ps; the other three focus on training and awareness of the personnel involved in the experiment, protective equipment and work practices, and factors associated with the place (or facility) where the research will be conducted. Animal handlers comprehension and knowledge determine the success of any containment program, and so this review also includes a discussion of critical teaching points for animal handlers and of the importance of evaluating personnel to verify their proficiency and competence in required protocols.