Antibacterial resistance has changed therapy of rhinosinusitis substantially, especially in patients who are moderately-severely ill. These patients are more likely to be infected with organisms that have changed dramatically in the last ten years in terms of susceptibility to older agents, such as aminopenicillins, amoxicillin, sulfadrugs, tetracyclines and more recently macrolides. Clinicians have also recognized that the incidence of b-lactamase production in H. influenzae and M. catarrhalis and multi-DRSP is sufficiently high to cause concern over the use of macrolides and aminopenicillins. Five years previously, oral cephalosporins were thought to be effective in this situation, but this is no longer the case, with no oral cephalosporins consistently able to treat fully resistant S. pneumoniae. Amoxicillin can be given in such cases but it must be given in a much increased dose and because of the consistent activity of the respiratory fluoroquinolones, like levofloxacin, there has been a renewed interest in using more potent agents against these infections.