The potential role of the commercially available fluoroquinolones in the treatment of Gram-positive infections is discussed on the basis of data obtained from animal experiments and clinical trials. In respiratory tract infections, and particularly in community-acquired pneumonia, it is evident that the presently available quinolones cannot be prescribed empirically as first-line therapy because of their borderline activity against Streptococcus pneumoniae and anaerobes. Reports of pneumococcal seeding in other tissues during quinolone therapy render their administration a debatable issue. Experience in endocarditis is limited to the use of ciprofloxacin plus rifampicin in intravenous drug users with right-sided Staphylococcus aureus endocarditis. Patients with staphylococcal osteomyelitis are included among cases of other bone infections. In noncontrolled studies ciprofloxacin, ofloxacin and pefloxacin attained a staphylococcal eradication rate ranging from 70 to 100%, while the addition of rifampicin has been proven to reduce the emergence of resistant mutants during therapy. In soft tissue and skin structure infections that also involve Gram-negative bacteria, ciprofloxacin and ofloxacin eradicated 72.6 and 89% of staphylococci, respectively; however, the presence of diabetes or vascular disease compromised the success of treatment. In staphylococcal peritonitis complicating continuous ambulatory peritoneal dialysis, results with ciprofloxacin given intravenously or intraperitoneally were promising. In infections in neutropenic hosts, success of prophylaxis or therapy is still not clear, since colonisation and breakthrough bacteraemias with viridans streptococci and staphylococci have been reported. Furthermore, therapeutic results are compromised by the low response rate in Gram-positive infections. Despite the reported clinical efficacy of the newer fluoroquinolones, physicians should be alerted to the emergence of staphylococci resistant to fluoroquinolones, mainly methicillin-resistant variants.