Lysosomes are membrane‐bound cytoplasmic organelles involved in intracellular protein degradation. They contain an assortment of soluble acid‐dependent hydrolases and a set of highly glycosylated integral membrane proteins. Most of the properties of lysosomes are shared with a group of cell type‐specific compartments referred to as ‘lysosome‐related organelles’, which include melanosomes, lytic granules, MHC class II compartments, platelet‐dense granules, basophil granules, azurophil granules, and Drosophila pigment granules. In addition to lysosomal proteins, these organelles contain cell type‐specific components that are responsible for their specialized functions. Abnormalities in both lysosomes and lysosome‐related organelles have been observed in human genetic diseases such as the Chediak‐Higashi and Hermansky‐Pudlak syndromes, further demonstrating the close relationship between these organelles. Identification of genes mutated in these human diseases, as well as in mouse and Drosophila pigmentation mutants, is beginning to shed light on the molecular machinery involved in the biogenesis of lysosomes and lysosome‐related organelles.—Dell'Angelica, E. C., Mullins, C., Caplan, S., Bonifacino, J. S. Lysosome‐related organelles. FASEB J. 14, 1265–1278 (2000)