INTRODUCTION: Although the life expectancy for patients with cystic fibrosis (CF) has increased dramatically in the preceding decades, often the final therapeutic option for patients with end-stage CF is lung transplantation. Prior to transplantation, patients with severe disease may require mechanical ventilation. Those refractory to mechanical ventilation may require extracorporeal membrane oxygenation (ECMO). The purpose of this case report is to describe the physical therapy management of a patient who received ECMO as a bridge to lung transplantation. CASE PRESENTATION: A 16-year-old girl with severe acute respiratory failure due to a CF exacerbation eventually required ECMO to maintain adequate gas exchange. While on ECMO, she received physical therapy interventions ranging from therapeutic exercise, manual therapy, and integumentary protection techniques in addition to airway clearance techniques. Prior to her transplant, she was standing multiple times per day with moderate assistance, was sitting on the edge-of-bed, as well as taking steps to transfer to/from a chair. She successfully received a bilateral lung transplant after 8 days on ECMO. CONCLUSION: Physical therapy interventions, including out-of-bed mobility, can be safely provided to patients on portable ECMO as a bridge to lung transplantation. These interventions were focused on preventing the negative sequelae of bed rest, increasing her strength and endurance, as well as improving her level of consciousness and psychological well being in preparation for lung transplantation.