Generalized lymphatic anomaly (GLA) and Gorham-Stout disease (GSD) are related diseases involving the lymphatic vasculature. Patients with these diseases frequently develop chylothorax, which can cause respiratory distress, failure, and death. Unfortunately, the optimum treatment for GLA and GSD patients with chylothorax remains unknown. Here we review 64 previously reported cases of chylothorax in GLA and GSD and describe a GLA patient with bilateral chylothorax that was treated with a pleurovenous shunt after multiple other treatments failed. Unfortunately, this shunt was not able to control the patient’s effusion, and she succumbed to her disease 3 years after the shunt was placed. Interestingly, our literature review revealed that patients with left-sided effusions had better outcomes than patients with either right-sided or bilateral effusions. Taken together, our report highlights the difficulty in managing chylothorax in patients with GLA or GSD and reveals that a better understanding of the cause of chylothorax is needed so that new therapies can be developed to treat this common complication of GLA and GSD.