Antimicrobial resistance is a growing problem among pathogens from respiratory tract infections. b-Lactam resistance rates are escalating among Streptococcus pneumoniae and Haemophilus influenzae. Macrolides are increasingly used for the treatment of respiratory tract infections, but their utility is compromised by intrinsic and acquired resistance. This article analyses macrolide-resistance mechanisms and their worldwide distributions in S pneumoniae, S pyogenes, and H influenzae.