Chronic osteomyelitis is a multifaceted bacterial infection with common features, which requires surgery for remission. The duration and modality of concomitant administration of antibiotic agents for adult patients is still based on expert opinions. The traditional recommendation of 6 to 12 weeks of antibiotic therapy with intravenous administration for at least the first 2 weeks is more and more challenged in favor of an oral antibiotic treatment with selected agents from the start. There is no evidence that the total duration of antibiotic therapy for more than 6-12 weeks improves outcome, when compared with shorter regimens. External advice from an expert team with combined surgeons and infectious disease physicians may help to reduce antibiotic consumption in a cost-effective way.