Objective: To review the mechanisms of action of macrolides in pediatric respiratory diseases and their clinical indications. Sources: Review in the PubMed database, comprising the following terms in English: “macrolide and asthma”; “macrolide and cystic fibrosis”; “macrolide bronchiolitis and viral acute”; “macrolide and bronchiolitis obliterans”; and “macrolide and non‐CF bronchiectasis”. Summary of the findings: The spectrum of action of macrolides includes production of inflammatory mediators, control of mucus hypersecretion, and modulation of host‐defense mechanisms. The potential benefit of macrolide antibiotics has been studied in a variety of lung diseases, such as cystic fibrosis (CF), bronchiectasis, asthma, acute bronchiolitis, and non‐CF bronchiectasis. Several studies have evaluated the benefits of macrolides in asthma refractory to therapy, but the results are controversial and indications should be limited to specific phenotypes. In viral bronchiolitis, there is no consistent benefit in acute conditions, although recent data have shown an effect in recurrent wheezing prevention. In patients with CF results are also contradictory, but the consensus states there is a small clinical benefit, especially for patients infected with P. aeruginosa. There was also no positive action of macrolides in patients with post‐infectious bronchiolitis obliterans. Children with non‐CF bronchiectasis seem to have clear benefits regarding the use of macrolides, which showed clinical advantages in parenchyma protection and lung function. Conclusions: The long‐term use of macrolides should be limited to highly selected situations, especially in patients with bronchiectasis. Careful evaluation of the benefits and potential damage are tools for their indication in specific groups.