The development of fluoroquinolones (FQs) with enhanced activity against Streptococcus pneumoniae is a potential advance in the treatment of pneumococcal infections, particularly those due to beta-lactam-resistant pneumococci. However, FQ-resistant clinical isolates selected by the older FQs have already been reported, with mutation(s) in both FQ targets conferring cross-resistance to newer FQs. It is likely that recombinational events between topoisomerase genes from related species of streptococci contribute to the spread of FQ resistance in S. pneumoniae. A scenario resembling that of the worldwide spread of resistance to beta lactams should be anticipated.