Mixed cryoglobulinemia (MC) and glomerulonephritis are the most important extrahepatic manifestations of chronic hepatitis C virus (HCV) infection. The clinical expression of cryoglobulinemia varies from an indolent course to the development of systemic vasculitis. The renal manifestations may range from isolated proteinuria to overt nephritic or nephrotic syndrome with variable progression towards chronic renal insufficiency. Plasmapheresis appears to be a useful adjunct to conventional therapy in the treatment of anti-GBM nephritis, severe dialysis-dependent forms of pauciimmune RPGN, cryoglobulinemia, and HUS-TTR Therapy with plasmapheresis produced a marked decrease in cryoglobulin levels and a subsequent relevant clinical improvement of cutaneous lesions and renal function. In cryoglobulinemia, plasmapheresis can be used as effective further therapy to minimize cutaneous, renal and/or neurologic involvement.