Cathepsins B, H, and L, representative lysosomal cysteine proteinases, have been shown to be involved in the degradation of proteins, generation of bioactive proteins, antigen processing, etc. Recent biochemical as well as Immunohisto/cytochemical studies have demonstrated that these enzymes are transferred from the trans Golgi network to lysosomes of cells, and in some cases, to secretory granules of certain endocrine cells, or they are secreted from cells. Localization of these enzymes in lysosomes differs depending on cell types even in the same tissues, suggesting that expression of these enzymes is regulated corresponding to cell specialization. Cathepsins B and H are localized in secretory granules of some peptide hormone-producing cells; particularly, cathepsin B is co-localized with renin in various endocrine cells producing active renin, indicating that cathepsin B is a major candidate of the renin converting enzyme. Moreover, these cysteine proteinases are secreted as their pro- or active forms from various tissue cells. In the resorption lacuna facing osteoclasts, secreted cathepsin L has been suggested to play a major role in the degradation of organic bone constituents, particularly collagen. Thus cathepsins B, H, and L act as biomodulators in various cells and tissues. In the present review, we introduce the precise localization of cathepsins B, H, and L and discuss their possible roles in cells and tissues.