The association between hepatitis C virus (HCV) infection and type 2 diabetes (T2D) has been known for over 20 years. Cross-sectional and longitudinal studies have shown a higher prevalence and incidence, respectively, of T2D in patients with chronic HCV infection. HCV induces glucose metabolism alterations mostly interfering with the insulin signaling chain in hepatocytes, although extrahepatic mechanisms seem to contribute. Both IR and T2D accelerate the histological and clinical progression of chronic hepatitis C as well as the risk of extra-hepatic complications such as nephropathy, acute coronary events and ischemic stroke. Before the availability of direct-acting antivirals (DAAs), the therapeutic choice was limited to interferon (IFN)-based therapy, which reduced the incidence of the extra-hepatic manifestations but was burdened with several contraindications and poor tolerability. A better understanding of HCV-associated glucose metabolism derangements and their reversibility is expected with the use of DAAs.