The purpose of this paper was to review our clinical experience in patients with osteomyelitis (OM) of the jaw, focusing on aspects of antimicrobial resistance. A retrospective review of the medical records of adult patients with jaw OM was carried out. Among 46 cases of jaw OM, the cause was odontogenic in 32 (seven had recent dental implants and four bisphosphonate osteonecrosis), postoperative/post-traumatic in eight, and secondary to osteoradionecrosis in six. Clinical features were chronic in 91.3%. The infection was polymicrobial in 24/41 (65.9%). Viridans streptococci were the most commonly isolated agents. Among 26 viridans streptococci tested, 81% were susceptible to penicillin and 96% to fluorquinolones, but only 11.5% to clindamycin. Overall, 35/38 (92.1%) had at least one clindamycin-resistant isolate. Appropriate antibiotics were administered for a mean of 5.8 +/- 3.2 months. Beta-lactams were used in 19 cases and fluorquinolones in 14. Among 39 cases with long-term follow-up, only two relapsed. Currently, jaw OM is commonly related to osteoradionecrosis, dental implants, and bisphosphonates. In patients with prior antibiotics exposure, a high percentage of infections were caused by clindamycin-resistant microorganisms, thus, beta-lactams should be the antibiotic of choice. In penicillin-allergic cases, the new fluorquinolones, probably in combination with rifampin and/or clindamycin, could be a promising alternative.