The present review provides an updated critical analysis of the use of quinolones in osteomyelitis and orthopaedic prosthetic infections. 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 noncomparative studies. Local drug carriers impregnated with quinolones allow high local antibiotic concentrations to be achieved in experimental systems. Considerable clinical experience has been gained mostly with ciprofloxacin and ofloxacin. Cumulated results in clinical trials show clinical success rates of more than 90% in osteomyelitis caused by Enterobacteriaceae. The combination of quinolones and rifampicin for the treatment of staphylococcal osteomyelitis as well as orthopaedic prosthetic infections appears very promising in clinical studies with a small number of patients. However, further comparative studies using quinolones as single agents or in combination (versus standard parenteral therapy) remain necessary in osteomyelitis due to Staphylococcus aureus or Pseudomonas aeruginosa. In particular, studies with the newer quinolones should be strongly encouraged in acute or chronic osteomyelitis and in more complicated situations such as diabetic osteomyelitis or foreign-body infection.