Microbial control agents offer a method of pest control using organisms that are a natural component of the environment and are usually much more selective than chemical pesticides. Furthermore, they can usually be integrated with other methods of control, and may provide prolonged control by establishment within the host population. However, microbial control agents also possess properties that can pose human and environmental risks depending on the nature of the pathogen and its pattern of use. We present an overview of issues concerning the safety and registration of microbial control agents with emphasis on pathogens of locusts and grasshoppers. The potential safety issues and other consequences of concern from the deployment of microorganisms for pest control are: (1) pathogenicity to non-target organisms, (2) toxigenicity to non-target organisms, (3) competitive displacement of microorganisms, and (4) allergenicity. Inundative control methods pose unique risks because the pathogens must be produced in large quantities, stored, transported, and applied, usually in concentrations much higher than would normally ever occur naturally. The overriding concern in introducing an exotic agent is the risk to non-target beneficial organisms, because once the agent becomes established, it will in most situations be impossible to eradicate. However, if indigenous organisms are used, there is relatively little risk of irreversible, long-term detrimental effects. A synopsis of safety testing results of some of the more promising microbial control agents for grasshoppers and locusts and an evaluation of their potential hazards are presented. Safety to vertebrates is evaluated by a tiered series of laboratory test requirements. Assessments on hazards to non-target invertebrates are based principally on results of laboratory bioassays. Safety tests should be chosen with regard to the biological characteristics of the agent and should not impose standards that are more stringent than those imposed on other forms of pest control. Regulatory oversight should assure the integrity of the environment and safety of the public, while at the same time not unduly hampering the development, registration, and use of more sustainable pest control methods.