The newer fluoroquinolones have many properties such as safety, bioavailability, and tissue penetration that make them attractive in the therapy of complicated infections. Unfortunately, the rapid development of resistance by Staphylococcus aureus to ciprofloxacin has dampened interest in these agents for serious staphylococcal infections. A patient with right-sided methicillin-resistant Staphylococcus aureus (MRSA) endocarditis with a complicated clinical course received trovafloxacin in addition to vancomycin and rifampin. He was initially treated with vancomycin, gentamicin, and rifampin for serious MRSA infection, but because of complications, including septic central nervous system emboli, persistent fever, and leukocytosis, gentamicin was stopped and trovafloxacin begun. After this addition the patient improved and completely recovered. In vitro and animal model data show that many newer fluoroquinolones have excellent activity against S. aureus, including MRSA, and are also less likely to induce resistance. Animal models of endocarditis support their efficacy in serious staphylococcal infections.