This review focuses on the relationship between hepatitis C virus (HCV) infection and glucose metabolism derangements. Cross-sectional and longitudinal studies have shown that the chronic HCV infection is associated with an increased risk of developing insulin resistance (IR) and type 2 diabetes (T2D). The direct effect of HCV on the insulin signaling has been analyzed in experimental models. Although currently available data should be considered as preliminary, HCV seems to affect glucose metabolism via mechanisms that involve cellular pathways that have been implicated in the host innate immune response. IR and T2D not only accelerate the histological and clinical progression of chronic hepatitis C, but also reduce the early and sustained virological response to interferon-alpha-based therapy. Thus, a detailed knowledge of the mechanisms underlying the HCV-associated glucose metabolism derangements is warranted, in order to improve the clinical management of chronic hepatitis C patients.