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Each year, approximately 55,000 individuals worldwide die from an infection due to the rabies virus. Rabies is a life-threatening disease caused by an RNA virus that is usually transmitted to humans through bites from rabid animals. More recently, reports of transmission by means of organ transplantation have been reported. Since human rabies is nearly 100% fatal if prophylactic measures are not followed, an increased awareness of who should receive prophylaxis and when prophylaxis should be administered is necessary. Preexposure prophylaxis entails the administration of the rabies vaccine to individuals at high risk for exposure to rabies viruses (e.g., laboratory workers who handle infected specimens, diagnosticians, veterinarians, animal control workers, rabies researchers, cave explorers). Preexposure prophylaxis involves a three-dose series of the rabies vaccine that may confer some protection from the virus while simplifying postexposure prophylaxis regimens. Postexposure prophylaxis consists of a multimodal approach to decrease an individual's likelihood of developing clinical rabies after a possible exposure to the virus. Regimens depend on the vaccination status of the victim and involve a combination of wound cleansing, administration of the rabies vaccine, and administration of human rabies immune globulin. If used in a timely and accurate fashion, postexposure prophylaxis is nearly 100% effective. Once clinical manifestations of rabies have developed, however, treatment options for rabies are limited, and to date, only seven individuals have survived rabies virus infection. Treatment of clinical rabies consists of medical support in an intensive care unit, using a multifaceted approach that includes supportive care, heavy sedation, analgesics, anticonvulsants, and antivirals. The recently developed Milwaukee Protocol added induction of therapeutic coma to supportive care measures and antivirals; however, its use has shown inconsistent outcomes.