Mixed cryoglobulinemia remains a major challenge to the clinician, both in terms of diagnosis and treatment. The discovery of its association with the hepatitis C virus has helped to shed light on the mechanisms of its pathogenesis and on how this complex disease might be managed. In this respect, interferon represents the first attempt to take an etiological approach to the treatment of a virus-related, immune-mediated human disease. Its uneven results, however, have on the one hand raised hopes that a final solution to the problem may be near, and at the same time underlined the fact that we probably have a long way to go before our goal is actually reached.