The most frequent kidney disease associated with chronic hepatitis C virus (HCV) infection is type I membranoproliferative glomerulonephritis (MPGN) in patients with type II mixed cryoglobulinemia. The principal clinical manifestations of glomerular disease in HCV-infected patients are the presence of proteinuria and microscopic hematuria with or without impaired kidney function. Various approaches have been tried for the treatment of HCV-associated glomerulonephritis, including immunosuppressive therapy (corticosteroids and cytotoxic agents), plasma exchange and antiviral agents. Limited data exist regarding antiviral treatment of HCV-associated glomerulonephritis, whereas immunosuppressive agents have been suggested for cryoglobulinemic kidney disease. A recent meta-analysis of controlled clinical trials (CCTs) suggested that standard interferon (IFN) doses were more effective than immunosuppressive agents in lowering proteinuria of patients with HCV-related cryoglobulinemic glomerulonephritis (odds ratio 3.86; 95% confidence interval, 1.44-10.33; p=0.007). However, data for follow-up were not given. Two distinct approaches should be considered for the treatment of HCV-associated cryoglobulinemic glomerulonephritis according to the level of proteinuria and kidney failure. Preliminary studies with rituximab therapy of HCV-related cryoglobulinemic glomerulonephritis have given encouraging results, even if a point of caution is important, because rituximab use may be associated with activation of various infections, including HCV.