Cryoglobulinemic vasculitis, also termed mixed cryoglobulinemic syndrome, is a rare systemic small vessel vasculitis due to the vascular deposition of immune- complexes, mainly mixed IgG-IgM cryoglobulins. It is associated with hepatitis C virus infection, immunological, and neoplastic diseases. Cryoglobulinemic vasculitis is characterized by the classical triad of purpura, weakness and arthralgia, frequent multiple organ involvement, and with infrequent late lymphatic and hepatic malignancies. The etiopathogenesis of cryoglobulinemic vasculitis is not completely understood. However, hepatitis C viral infection and associated lymphotropism, genetic and environmental factors play important roles in cryoglobulin and immune-complex production that deposit in blood vessels, and in B-lymphocyte expansion. The diagnosis is suggested by clinical evidence of purpura, circulating mixed cryoglobulinemia and low C4 levels, and pathologically evident leukocytoclastic vasculitis in skin biopsy lesions. The prognosis is poor in patients with renal disease, liver failure, and malignancy. Treatment is directed toward eradicating hepatitis C viral infection employing combination PEGylated- interferon-alpha and ribavirin treatment, immunomodulatory and immunosuppressant medications as warranted by the level of clinical severity.