SiR-lysosome is based on the cathepsin D binding natural product pepstatin A. SiR-lysosome is fluorogenic, cell permeable and highly specific for lysosomes. Sir-lysosome stains lysosomes in ilve cells without the need for genetic manipulation or overexpression. Its emission in the far red minimizes phototoxicity and sample autofluorescence. SiR-lysosome is compatible with GFP and/or m-cherry fluorescent proteins. It can be imaged with standard Cy5 filtersets. SiR-lysosome can be used for widefield, confocal, SIM or STED imaging in living cells and tissue.