An adult 175 g imported panther chameleon, Furcifer pardalis, was presented with a three month history of an open wound on the ventral, rostral mandible. Previous treatments were oral enrofloxacin, and topical application of hydrogen peroxide and an OTC antibiotic preparation. Husbandry and diet appeared adequate and the chameleon was alert with good body condition. Physical examination revealed missing teeth, firm swellings of the rostral and left hemimandibles, an open wound on the rostroventral mandible and symphyseal luxation. Empirical initial treatment included chlorhexidine rinse to the open wound, and cephelexin and metronidazole orally. Metabolic, thermal, and humidity needs were also addressed. On CBC, a large microfilaria and a monocytosis were identified. Radiographically, proliferative lesions were noted in both hemimandibles. Histologic evaluation of bone biopsy yielded numerous branching septate hyphae suggestive of Aspergillus spp.. Acinetobacter spp. sensitive to amikacin and gentamicin was cultured from the wound. Itraconazole orally and amikacin intramuscularly for 45 days was instituted. Anesthesia was induced with propofol IV and maintained via isoflurane at 0.5 - 1.5% to allow surgical debridement and symphyseal pin placement. Two weeks postoperatively, 60% of the chameleons tongue sloughed. At six month, follow up the owner reports the animal to be thriving although it cannot prehend prey normally necessitating hand feeding. Multiple factors such as chameleon disposition, periodontal anatomy, and husbandry may contribute to periodontal osteomyelitis in chamaeleonids. Accurate diagnosis and appropriate, aggressive treatment are key in successful outcome of these cases.