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Non-cystic fibrosis bronchiectasis is a chronic disorder in which immune system dysregulation and impaired airway clearance cause mucus accumulation and consequent increased susceptibility to lung infections. The presence of pathogens in the lower respiratory tract causes a vicious circle resulting in impaired mucociliary function, bronchial inflammation, and progressive lung injury. In current guidelines, antibiotic therapy has a key role in bronchiectasis management to treat acute exacerbations and chronic infection and to eradicate bacterial colonization. Contrastingly, antimicrobial resistance, with the risk of multidrug-resistant pathogen development, causes nowadays great concern. The aim of this literature review was to assess the role of antibiotic therapy in bronchiectasis patient management and possible concerns regarding antimicrobial resistance based on current evidence. The authors of this review stress the need to expand research regarding bronchiectasis with the aim to assess measures to reduce the rate of antimicrobial resistance worldwide.