Osteomyelitis can result from hematogenous or contiguous microbial seeding of the bone. Staphylococcus aureus is the most common infecting microorganism. Although any bone can potentially develop osteomyelitis, long-bone, vertebral, and foot osteomyelitis account for the majority of cases. Confirmatory diagnosis of osteomyelitis often depends on the results of a bone biopsy and bone cultures. Radiologic and laboratory studies are often helpful in leading to the diagnosis, determining the extent of the disease, and following up selected patients with osteomyelitis. Optimal therapy for osteomyelitis requires the collaboration of a multidisciplinary team of physicians. Debridement is often needed in contiguous osteomyelitis, whereas acute hematogenous and vertebral osteomyelitis can often be treated with a prolonged course of antimicrobial therapy.