Osteomyelitis is an ancient disease with varied pathophysiology. The several clinical syndromes associated with bone infection have specific clinical presentations and microbiology. Successful recognition and management of the disease requires a knowledge of these mechanisms and the organisms most common in each. Diagnosis is made by a combination of clinical examination, supportive blood testing, and appropriate radiography. With these elements in place, patient presentation can be placed in the framework of a staging system, which often helps to suggest the appropriate mix of antimicrobial and surgical therapies.