Background: India contributes to 32% of the total global disability-adjusted life years, due to chronic respiratory diseases. This has led to a high rate of health loss from these diseases. Antibiotics are commonly used in the management of respiratory disorders. With excellent tissue penetration, prolonged tissue persistence, and favorable side effect profile, macrolides are one of the best treatment options being recommended for respiratory, urogenital, dermal, and other bacterial infections. Still, there is a lack of clinical trial data on the use of macrolides in the management of respiratory chronic disease, and hence, there is a need for clinical guidance on their use in Indian setting. Methods: A systematic review of the literature was conducted on PubMed, Cochrane database, and Google Scholar. Existing guidelines, meta-analyses, systematic reviews, randomized controlled trials (RCTs), non-RCTs, landmark studies, and key-cited articles were selected. Recommendations were based on available evidence and expert panel's logical empiricism and consensus. Results and Discussion: This article discusses evidence-based and clinical practice based management of chronic respiratory conditions including chronic obstructive pulmonary disease, asthma, bronchiectasis, diffusive panbronchiolitis, and organizing pneumonia. The authors reviewed different respiratory conditions, role of macrolides in their management, adverse events and antimicrobial resistance associated with macrolides, evidence review of various clinical trials, guideline recommendations, and clinical recommendations.