Several newer fluoroquinolones, which have been recently introduced or are under investigation, display substantially greater potency against Gram-positive organisms than the older generation agents of this class. Nevertheless, for problem organisms including methicillin-resistant strains of Staphylococcus aureus and many Enterococcus faecium, concentrations of newer antimicrobials required to inhibit 90% of organisms in the collections studied remain above those that are projected to be achievable with clinical use. Nevertheless, enhanced potency of several newer quinolones may result in a favourable pharmacodynamic profile leading to improved outcomes against Gram-positive infections and possibly to the delayed or diminished emergence of resistance to these agents.