A number of experimental studies have provided evidence that several classes of antibiotics exert actions that modulate inflammatory cell function, beyond their direct antibacterial activities. The immunomodulatory effects of antibiotics on leukocytes may be either stimulatory or inhibitory and seem to be related to the activation state of the leukocytes, facilitating bacterial keeling and resolution of local inflammation. Although quinolones exhibit some immunomodulatory effects, the macrolides have been investigated most extensively. The immunomodulatory actions of antibiotics include accumulation in inflammatory cells, effects on leukocyte adhesion, migration, function and cytokine expression and effects on bronchial epithelial cells and mucus secretion. The clinical implications and possible therapeutic benefits of these effects have been studied in various respiratory inflammatory disorders, including communityacquired pneumonia, chronic obstructive pulmonary disease, asthma, bronchiectasis, cystic fibrosis and diffuse panbronchiolitis. Pneumon 2008; 21(1):33–44