Bronchiectasis is a constellation of diseases characterized by abnormally dilated bronchi with thickened bronchial walls due to repeated infection and inflammation. Bronchiectasis causes impairment of mucociliary clearance, airflow limitation, bronchorrhea, and predisposes to recurrent respiratory infections. It has a number of potential underlying causes. Laennec first described bronchiectasis as a distinct clinical entity in 1819 (Barker 2002, O’Donnell 1998). The diagnosis, investigation and particularly management of bronchiectasis has been largely empirical and unfortunately, the subject of relatively few controlled clinical trials. Cystic fibrosis causes about a third of all bronchiectasis in United States (O’Donnell 1998), and is common worldwide. Cystic fibrosis (CF) is a recessive genetic disease characterized by dehydration of the airway surface liquid and impaired mucociliary clearance caused by altered functioning of a chloride channel called the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). Impaired chloride conductance through the apical portion of airway cells leads to dehydration of airway secretions causing lung destruction through obstruction of the airways with thickened secretions. The resultant endobronchial infection and exaggerated inflammatory response leads to the development of bronchiectasis (destruction and widening of airways) and progressive obstructive airway disease. This chapter provides insight into the specific diagnostic and therapeutic roles of bronchoscopy in patients with bronchiectasis and Cystic Fibrosis.