Background: Brown recluse spider bites cause significant trauma via their tissue toxic venom. Diagnosis of these injuries and envenomation is difficult and many times presumptive. Treatment is varied and dependent upon presentation and course of injury. Materials and Methods: We present a case of a previously unreported incidence of osteomyelitis of the mandible as a result of a brown recluse spider bite. A review of the literature and discussion of diagnosis and treatment of brown recluse spider bites are presented. Results: Osteomyelitis of the mandible causing a chronic wound was the presenting finding of a patient with a history of spider bite and exposure to brown recluse spiders. Operative debridement and wound closure resulted in successful treatment. Brown recluse spider envenomation varies in its presentation and treatment is based on the presenting clinical picture. Conclusion: Treatment regimens for brown recluse spider bite envenomation should include the basics of wound care. Systemic antibiotics, topical antimicrobials, dapsone, and surgical debridement are valuable adjuncts of treatment, as indicated, based on the clinical course.