Various defects in host immunity predispose a patient to the development of bronchiectasis. The human immunodeficiency virus and hypogammaglobulinemia are two classic examples of host defects resulting in bronchiectasis. Recommendations for work up and therapy in these diseases are discussed. Hyper-immunoglobulin E syndrome has a significant association with bronchiectasis and pulmonary pathology. Antigen processing deficiency and dysregulated adaptive immunity to Pseudomonas bacteria are both specific immune deficits that can result in hyperactivity of innate immunity. These interactions are best described as “immune dysregulation,” and may be responsible for the true pathogenesis of bronchiectasis. With continued clarification of these mechanisms, there may be hope for future-directed therapies and vaccinations in the management of bronchiectasis. In summary, this paper highlights the concomitant nature of bronchiectasis and immunodeficiency and emphasizes the importance of a thorough evaluation and therapy of one when the other is present.