Protein losing enteropathy (PLE) has emerged as an increasingly common complication of single ventricle palliation in children born with cyanotic congenital heart disease. This entity becomes manifest months or years after the modified Fontan operation and is thought to affect 5-15% of all patients with Fontan physiology. Patients with PLE often suffer from symptoms related to severe hypoproteinemia and intestinal malabsorption, including edema, ascites, pleural and pericardial effusions, chronic diarrhea and poor growth. Mortality is strikingly high, with only 50% of patients surviving for more than 5 years following diagnosis. The pathophysiology is poorly understood and several theories are presented as possible mechanisms which includes: 1) chronic low cardiac output and intestinal injury leading to loss of intestinal integrity, 2) chronic intestinal inflammation leading to loss of intestinal integrity, 3) chronic elevated portal venous pressure with intestinal injury leading to loss of intestinal integrity. Treatment is sporadically successful and has included 1) creating a fenestration between the Fontan pathway and pulmonary venous atrium which decreases Fontan pressure and increases cardiac output, 2) chronic use of unfractionated or low molecular weight heparin to reconstitute the intestinal basement membrane, 3) Use of oral steroids to reduce intestinal inflammation, 4) Use of pulmonary vasodilators to reduce Fontan pressure and increase cardiac output 5) implantation of pacemakers to treat sinus node dysfunction and improve cardiac output, 6) heart transplantation. Short of cardiac transplantation, no treatment of PLE, including efforts to change systemic and/or gastrointestinal hemodynamics, is routinely successful. Thus, it appears that the etiology of PLE is more complex than simply "high venous pressure in the gut" as has been previously believed.