Many antibiotics, including macrolides and quinolones, are used incorrectly in the treatment of presumed respiratory tract infections. The use of broad-spectrum antibiotics increased considerably in the 1990s, but often this use is inappropriate. Guidelines, such as those for community-acquired pneumonia, encourage rational therapy and more prudent prescribing. There are strong links between appropriate use, compliance and resistance as well as between regimen complexity and compliance. These issues provide a platform for thinking about a short-duration, high-compliance drug therapy with good clinical efficacy. Such therapy will need to be combined with programs to promote rational antibiotic use, particularly targeting inappropriate prescribing for viral infections and use of agents with a broader antimicrobial spectrum than is necessary.