This chapter focuses on the most well characterized inhibitors—cystatin C—and provide some information on its structure, biochemical properties, its role in normal and abnormal physiological processes, as well as on its use as a diagnostic marker. A major part of the cysteine proteases are evolutionary related to the structurally well–defined cysteine protease papain and are called papain–like cysteine proteases. The biological roles and the cystatin superfamily inhibitors of papain–like cystein proteases are also discussed. The aminoacid sequence and schematic structure of human cystatin C is also presented. The evolutionary relationships among all known inhibitory active human cystatins and kininogen cystatin domains are diagrammatically represented. The distribution of cystatins in body fluids and additional functions attributed to cystatin C are described. The serum or plasma cystatin C is used as a marker for glomerular filtration rate (GFR). The urine cystatin C is used as a marker for proximal tubular damage. The two types of brain hemorrhage associated with Cystatin C amyloid deposits are also demonstrated. The conditions connected with deposition of amyloid β–protein in cystatin C and cerebral hemorrhage is also provided.