Mandibular osteomyelitis is caused most commonly by members of the oral flora in the setting of dental infection or dental manipulation, often in patients with underlying mandible pathology. Recognizing and treating mandible infections is especially challenging when they are associated with osteonecrotic conditions that are themselves difficult to manage and that may be associated with symptoms and testing results that mimic infection. Optimized diagnosis and management of mandible infections require collaboration between specialists in surgical and medical aspects of care, with the goal of clearing or controlling infection while maximizing function.