An eight-year-old girl with cystic fibrosis (CF) developed a left upper lobe collapse failing to resolve with initial conventional antibiotic treatment, mucolytics and intensified physiotherapy. Mycobacterium abscessus was isolated from her sputum. Bronchoscopy revealed thick viscous mucus plugging of the left upper lobe bronchus with complete obliteration. Three bronchoscopies with saline lavage and Dornase alfa, a rhDNase, at the end of each procedure resulted in removal of this mucus plug and the re-inflation of the affected lobe, with clinical and radiological resolution. The use of flexible bronchoscopy as a ‘secondary’ treatment with 0.9% saline lavage and instillation of rhDNase is described sparsely in the literature. This is the first reported successful therapeutic resolution of a lung collapse in a CF patient with Mycobacterium abscessus, with sequential therapeutic bronchoscopies with instillation of Dornase alfa. This should be considered for lobar collapse in CF not responding to the standard therapeutic regime.