We report the use of independent lung ventilation (ILV) in a patient with severe underlying parenchymal disease who developed bronchopleural fistula (BPF) after thoracotomy and decortication of an empyema with subsequent development of acute respiratory distress syndrome (ARDS). While a great majority of patients with either ARDS or BPF can be successfully managed with conventional ventilation strategies, the additional management challenges presented by BPF in the setting of ARDS and sepsis often necessitate the utilization of alternative ventilation strategies such as ILV, high frequency ventilation (HFV), and extracorporeal support.