Chronic osteomyelitis is a multifaceted bacterial infection with common features. It absolutely requires surgery for remission. The duration and form of concomitant administration of antibiotic agents for adult patients is still based on expert opinion. The traditional recommendation of 6-12 weeks of antibiotic therapy, where, for at least the first 2-6 weeks, antibiotics should be administered intravenously, 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 4-6 weeks improves outcome, when compared with shorter regimens. Hopefully, the future will show randomized trials in the adult population, allowing optimal timing of surgical and medical therapy and sparing of unnecessary prescription, with concomitant development of antibiotic resistance. External advice from an expert team with combined surgeons and infectious disease physicians may help to reduce antibiotic consumption in a cost-effective way.