This chapter summarizes the numerous causes of non-cirrhotic portal hypertension and differentiates them histologically and clinically from the most common cause of portal hypertension, cirrhosis. Liver biopsy is always necessary to make the diagnosis of non-cirrhotic portal hypertension. Emphasis is placed on the increasingly more commonly diagnosed causes of non-cirrhotic portal hypertension, nodular regenerative hyperplasia and obliterative portal venopathy.