The present review provides a critical quantitative analysis of the use of quinolones in osteomyelitis. Only papers published in peer-reviewed journals and related to the following areas were selected: experimental osteomyelitis, penetration of quinolones into human bone and clinical use in comparative and non-comparative studies. Cumulated results show clinical success rates of more than 90% in osteomyelitis caused by Enterobacteriaceae, after prolonged oral use of ciprofloxacin. However, further comparative studies using oral quinolones as single agents or in combination (versus standard parenteral therapy) are required in osteomyelitis due to S. aureus or P. aeruginosa, or in more complicated situations such as diabetic osteomyelitis or foreign body infection.