This chapter focuses on important metabolic liver disease. Liver is affected in many metabolic diseases. However, the histomorphology is not very specific to these metabolic diseases. Most of the time, the liver histology shows presence of nonspecific steatosis in these disorders. In this chapter, we are highlighting those, metabolic disease, where the liver histology provides diagnostic clues. This chapter covers the erythropoietic protoporphyria, glycogen storage diseases (GSD), galactosemia, endoplasmic reticulum storage diseases (alpha 1-antitrypsin deficiency), lysosomal storage disease [glycosyl ceramide lipidosis (Gaucher disease)], sphingomyelin-cholesterol lipidosis (Niemann–Pick disease), Wolman and cholesterol ester storage diseases, and hereditary defects of bilirubin metabolism.