Respiratory infections are a major clinical problem, and treatment is increasingly complicated by the emergence of microbial antibiotic resistance. Development of new antibiotics is notoriously costly and slow; therefore, alternative strategies are needed. Antimicrobial peptides, central effector molecules of the immune system, are being considered as alternatives to conventional antibiotics. These peptides display a range of activities, including not only direct antimicrobial activity, but also immunomodulation and wound repair. In the lung, airway epithelial cells and neutrophils in particular contribute to their synthesis. The relevance of antimicrobial peptides for host defense against infection has been demonstrated in animal models and is supported by observations in patient studies, showing altered expression and/or unfavorable circumstances for their action in a variety of lung diseases. Importantly, antimicrobial peptides are active against microorganisms that are resistant against conventional antibiotics, including multidrug-resistant bacteria. Several strategies have been proposed to use these peptides in the treatment of infections, including direct administration of antimicrobial peptides, enhancement of their local production, and creation of more favorable circumstances for their action. In this review, recent developments in antimicrobial peptides research in the lung and clinical applications for novel therapies of lung diseases are discussed.