Cryoglobulinemia are immune complexes that may induce systemic cryoglobulinemic vasculitis. Cryoglobulin may be an isolated biological abnormality or may induce clinical manifestations of a systemic vasculitis, involving the skin, the joints, the peripheral nerve system and the kidneys.During the last 15 years, major advances have been obtained after the discovery of the hepatitis C virus, the main cause of cryoglobulins. Main factors associated with cryoglobulin production are female gender, alcohol intake above 50 g per day, extensive liver fibrosis and steatosis. Symptomatic cryoglobulins (i.e., vasculitis) are associated with older age, longer duration of infection and main characteristics of cryoglobulin itself (type II, IgM kappa, high serum levels). The pathophysiology is complex and involves humoral immunity, B and T cellular immunity, but not directly the virus itself. Peg-interferon-alpha and ribavirin combination leads to a virological and clinical response of the vasculitis in about 70% of patients. In non responders, recent open series suggested the efficacy of rituximab with a good response in up to 80% of patients, but a relapse in 42% seven months after the last infusion.New therapeutic strategies include a combination of best antiviral treatment with Peg-interferon-alpha plus ribavirin and rituximab. Multicenter controlled trials are mandatory.