For over 50 years, clinicians have known that macrolide antibiotics have effects on inflammation and the immune system that are not related to their antimicrobial properties. These immunomodulatory properties, best described for treating inflammatory airway diseases, protect the lung and the host and improve clinical status. This book summarizes our current knowledge regarding proposed mechanisms for these properties, established clinical results, and what the future may hold with emphasis on novel clinical applications and the fascinating development of non-antimicrobial macrolides with preserved and enhanced immunomodulatory properties.