Our understanding of the pathologic cycle leading to the development of bronchiectasis is enhanced by greater understanding of the genetic influences contributing to its development. Genome-wide linkage analysis, family-based genetic linkage studies, and the testing of candidate genes have all greatly advanced our understanding of the complexity of the genetic basis of bronchiectasis. This article discusses how allelic variations, gene modifiers, HLA associations, and the interplay of developmental, host, and environmental factors all contribute in lesser and greater degrees, depending on the specific disease, toward the development of bronchiectasis in a spectrum of disease processes.