A recent article published in Paediatric Respiratory Reviews stated that the first clinical indication of non-antibiotic benefits of macrolides was in adults with diffuse panbronchiolitis –characterized by chronic airway infection often with Pseudomonas aeruginosa; airway inflammation; bronchiectasis and a high mortality. Low dose erythromycin, and subsequently other macrolides, led in many cases to complete remission of the condition and eradicated the neutrophilic airway inflammation characteristic of the disease. This finding hinted towards the anti-inflammatory andimmunomodulatory effects of macrolides. Literature search disclosed that three trials of azithromycin in preschool wheeze gave contradictory results. A trial in pauci-inflammatory adult asthma and another in non-cystic fibrosis bronchiectasis both, showed a significant reduction in exacerbations, but none matched the dramatic results in diffuse panbronchiolitis. Furthermore, the increased risk of antibacterial resistance with macrolides persisted, when used widely and uncritically in children with respiratory disease.From the results, it was suggested that the pediatric respiratory community must refocus on the dramatic benefits of macrolides in diffuse panbronchiolitis; use modern-omics technologies to determine the endotypes of inflammatory diseases; and discover in nature or synthesize designer macrolides to replicate the diffuse panbronchiolitis results in children withrespiratory disease.