Chronic hepatitis C virus (HCV) infection causes progressive liver fibrosis, cirrhosis, liver failure, and hepatocellular carcinoma. Additional to liver damage, HCV infection causes a variety of systemic disorders, some of which sometimes bear more severe morbidity than the liver disease itself. These extrahepatic manifestations represent a wide spectrum of disorders, ranging from the presence of a variety of clinically insignificant autoantibodies to diseases affecting a variety of organ systems. Mixed cryoglobulinemia is a common manifestation, and associated vasculitis can affect many organs (kidney, skin, and joints). The skin can also be affected by porphyria cutanea tarda and lichen planus. Other common extrahepatic manifestations include autoimmune disorders, lymphoproliferative disorders, and a number of neurological and neuropsychiatric disorders such as fatigue, depression, or cognitive impairment. Insulin resistance, diabetes mellitus, accelerated atherosclerosis, and increased cardiovascular disease morbidity and mortality have also been associated with chronic HCV infection. The existence and severity of extrahepatic manifestations do not correlate with the severity of liver disease, and the mainstay of treatment is HCV eradication. Patients with systemic manifestations of HCV infection should be prioritized for treatment, especially in the era of new interferon-free therapies with fewer side effects.