Based on clinical, radiologic, and echocardiographic findings, a diagnosis of Group 5 PH associated with NF1 (PH-NF1) was made. Targeted PH therapy (endothelin receptor antagonists and phosphodiesterase-5 (PDE-5) inhibitors) was considered; however, due to limited evidence of benefit and potential risk in NF1-associated parenchymal lung disease, therapy was deferred in favor of conservative management with oxygen therapy and diuretics, and the patient was referred for pulmonary and cardiac rehabilitation. This evidence concerns the gene PDE5A and neurofibromatosis type 1.