The lysosomal system is the main intracellular mechanism for the turnover of endogenous and exogenous macromolecules. This catabolism is brought about in the lumen of lysosomes by a cocktail of predominantly hydrolytic enzymes with characteristic acidic pH-optima. The lysosomal membrane, which has a typical single phospholipid bilayer, controls the passage of material into and out of lysosomes, by its permeability and ability to fuse with digestive vacuoles or engulf cytosolic material. About 20 systems for transporting small molecules across the lysosomal membrane have been characterized but only two proteins, cystinosin and sialin, involved in the transport of cystine and sialic acid, respectively, have been cloned. A distinct, vacuolar proton pump (V-type H+ ATPase), which maintains the low luminal pH, has been characterized. Ubiquitous, highly glycosylated, integral membrane proteins of largely unknown function, called lysosome-associated membrane proteins (LAMPS) or lysosomal integral membrane proteins (LIMPS), account for about 50% of the protein in the lysosomal membrane. They have a short cytosolic domain of 10-20 amino acids containing single tyrosine or di-leucine motifs, which interact with adaptor complexes (APS) for sorting at the trans-Golgi network and targeting to lysosomes. A deficiency of LAMP-2 is the primary defect in Danon disease. Other proteins associate with the membrane transiently or cell-specifically. The structure, function and intracellular transport of these different classes of lysosomal membrane proteins will be reviewed.