After a long history of anti-infective therapeutic use, macrolide antibiotics have not yet given up all their secrets. Interest in their therapeutic potential in inflammatory diseases (possibly including non-infectious diseases) has generated abundant fundamental research and therapeutic trials worldwide. The main question regarding the future prospects of this class of drugs is whether some macrolides are beneficial in such settings because they modulate host inflammatory responses (and cellular targets) or rather because they eliminate a latent, unidentified pathogen which triggers chronic inflammation. However, no clearcut results have yet been obtained.