In cystic fibrosis (CF) patients, Gram-negative Burkholderia cepacia complex (Bcc) infections are associated with recurrent pulmonary exacerbations. Bcc organisms are innately resistant to many antibiotics, and infection with B. cenocepacia is a contraindication to lung transplantation. We report a CF patient with severe lung disease, colonized with Bcc, with a history of around nine exacerbations per year for over 10 years, for whom antibiotic regimens (including targeted and broad-spectrum antibiotics) had not cleared infection or extended the interval between exacerbations. After receiving a 2 week cefiderocol-containing regimen, the patient remained stable for more than 5 months without the need for additional antibiotics or hospital admissions for respiratory exacerbations.