We report on a 13-year-old girl with cystic fibrosis (CF) who developed refractory airflow obstruction despite high-dose steroids. She developed invasive aspergillosis and died despite oral and intravenous antifungal therapy. We speculate that the increasing use of immunosuppressive strategies and aggressive antipseudomonal therapy in CF may lead to an increase in aspergillus lung disease, including invasive aspergillosis in the future.