Hepatitis C virus (HCV) infection has been associated with multiple autoimmune manifestations. The immune response to HCV infection encompasses the development of autoantibodies, immune complex formation and deposition, and cryoglobulinemia complicated by vasculitis, glomerulonephritis, or neuropathy. HCV infection has been associated with antiphospholipid antibody syndrome, RA, SLE, PM/DM, and thyroid disease. HCV-infected patients also have a high incidence of sicca symptoms with sialoadenitis, and reports of low-grade lymphoproliferative malignancies have emerged. Optimal treatment for HCV-related autoimmune disease remains to be determined, but patients seem to respond to immunosuppression with classic agents or interferon.