Patients with non-cystic fibrosis bronchiectasis (NCFB) share many of the respiratory symptoms and the disease progression of cystic fibrosis (CF). As there are no approved therapies for the management of NCFB, an approach has been to use therapies similar to those used to treat CF. In many cases, however, this is ineffective or detrimental. The reason for this has not been determined, but it may be due to key differences in pathogenesis. The questions arising from this have spurred dedicated investigation into the effective management of NCFB. Patients with NCFB have chronic bacterial infection, and bacterial load correlates with symptoms and quality of life. Treatment with systemic antibiotics decreases bacterial load and can have a favorable effect on outcomes. Chronic or frequent use of systemic antibiotics, however, is impractical and sometimes unsafe, so aerosol as a means of delivery is seen as an attractive alternative. The clinical response to and tolerability of inhaled antibiotics have differed significantly between NCFB and CF. New delivery technology, novel antibiotic formulations and a better understanding of the bacterial burden of NCFB are now changing the approach to disease management.