Hepatitis C virus infection is a global public health issue that affects about 70 million people. Because of its hepatotropic and lymphotropic nature, which includes a wide spectrum of hepatic and extrahepatic manifestations, chronic hepatitis C infection is considered a systemic disease. Up to 80% of patients will develop at least one extrahepatic manifestation during the chronic phase of the disease; moreover, these manifestations could be the only symptom of hepatitis C infection. The most common extrahepatic manifestation is essential mixed cryoglobulinemia, whose progress can have a severe outcome as it affects the proliferation of B-lymphocytes which in turn could cause the development of B-cell non-Hodgkin’s lymphoma. More often the effect of mixed cryoglobulinemia is systemic vasculitis, on ground of which membranoproliferative glomerulonephritis may arise with an unpredictable course that can lead to end-stage kidney disease. In addition, patients with chronic HCV infection have a higher frequency of other extrahepatic manifestations including skin disoreders, autoimmune diseases, endocrine and cardiovascular and neuropsychiatric disorders that may worsen their prognosis and have a significant effect on the quality of their life. It is extremely important that clinicians consider the potential of HCV to cause extrahepatic manifestations in patients with chronic HCV infection, because an awareness of the range of potential extrahepatic manifestations could facilitate earlier diagnosis and a more appropriate and timely treatment of these disorders. This paper provides a brief overwiev of HCV-related extrahepatic manifestations with an emphasis on pathogenesis as well as systemic and organ-specific changes.