Cryoglobulins are immunogloblulins that persist in the serum, precipitate with cold temperature, and resolubilize when rewarmed. Mixed cryoglobulins, composed of different immunoglobulins, with a monoclonal component in type II and only polyclonal immunoglobulins in type III, are associated with connective tissue, malignant hematologic, or obvious infectious diseases. The syndrome of mixed cryoglobulinemia represents the consequence of an immune complex-type vasculitis. It is characterized by the clinical triad of purpura, arthralgia, and asthenia, and may involve numerous organs, particularly the peripheral nervous system and the kidneys. Mixed cryoglobulinemia frequently is associated with clinical and biologic evidence of liver disease. It seems fairly clear that mixed cryoglobulinemia is often a manifestation of underlying chronic active or persistent hepatitis. In the last 10 years, many studies have demonstrated that infection with hepatitis C virus is involved in the pathogenesis of most mixed cryoglobulinemia vasculitis. This review analyzes the main published data of hepatitis C virus-mixed cryoglobulinemia, the role of liver alterations, the predictive factors associated with mixed cryoglobulin production in hepatitis C virus patients and whether its character is symptomatic, and the different types of vasculitis associated with hepatitis C virus chronic infection and their treatments.