The human airways are protected from invading micro-organisms by the highly efficient innate immune system. Antimicrobial peptides that are produced by inflammatory cells and airway epithelial cells are key elements in this innate immune system. A major subgroup of the antimicrobial peptides is the family of defensins--small non-enzymatic and cationic peptides. Besides their extensively studied role in antimicrobial defense, recent studies have demonstrated that defensins are also able to modulate inflammatory responses, to stimulate adaptive immunity and contribute to tissue repair. In line with these observations, increased defensin levels were observed in inflammatory lung diseases, such as cystic fibrosis (CF), diffuse panbroncheolitis (DPB), idiopathic pulmonary fibrosis (IPF) and acute respiratory distress syndrome (ARDS), and in infectious diseases. In the past decade much has been learnt about the activity of defensins and there is abundant evidence for their presence in human inflammatory lung disease. Future studies are required to elucidate their role in the pathogenesis of these diseases.