Long-term macrolide therapy offers an evidence-based treatment to reduce frequent exacerbations in stable adult patients with bronchiectasis. There is limited evidence that these agents also attenuate the decline in lung function and improve health-related quality of life. The benefits and risks of long-term macrolide use need to be clearly explored for individual patients. Further work is needed to understand the optimal drug, dose, and regimen, the mechanisms behind these benefits, appropriate patient selection, sustainability of efficacy, potential long-term risk for the lung microbiome; and their use with or without inhaled antibiotic treatment. We reviewed the current evidence on long-term macrolides in adults with bronchiectasis.