Publisher Summary An estimated 7–10 billion laboratory tests of all types are performed each year in the USA alone. Very few others of those have a more direct effect on decisions critical to prevent human mortality than rabies laboratory tests. Rabies diagnostic evaluation is most frequently performed for the post-mortem examination of animals that have bitten a person or have otherwise potentially caused human exposure to the disease. These examinations constitute the most important diagnostic contributions to the control and prevention of rabies. Evidence of rabies virus infection, based on a positive diagnostic test, prompts administration of rabies post-exposure prophylaxis (PEP) to the exposed person, preventing the onset of the almost invariably fatal infection. Demonstration of rabies virus infection also initiates proper management of exposed domestic animals, including booster vaccination of previously immunized animals and euthanasia or quarantine of unvaccinated animals. Prompt and reliable negative results, on the other hand, can be used to prevent the initiation of unnecessary PEP in humans, avoiding the small but inherent associated risks and the squandering of expensive and often scarce biologics.