Epidemiological data clearly indicate a link between chronic hepatitis C (CHC) and disturbed glucose homeostasis. The prevalences of both type 2 diabetes mellitus (T2DM) and insulin resistance (IR) are higher among those chronically infected with hepatitis C when compared with the general population and those with other causes of chronic liver disease. Both IR and diabetes are associated with adverse outcomes across all stages of CHC including the liver transplant population. The adverse effects that directly influence patient outcome are reduced responsiveness to antiviral therapy, more rapid progression of fibrosis to cirrhosis and a higher incidence of hepatocellular carcinoma. Although both viral and host factors are known to contribute to IR (and therefore the risk of T2DM), there is a paucity of evidence to support interventions targeting IR with pharmacotherapy or lifestyle intervention. The purpose of this review is to examine the impact of abnormalities of glucose homeostasis in CHC, and in so doing, to raise a number of questions. How do we identify those at risk of diabetes in CHC? Can we reduce the incidence of hepatoma and reduce transplant-related morbidity and mortality by preventing or treating diabetes? Can we improve the response to antiviral therapy by pretreating IR and T2DM in treatment candidates? Ultimately, can we cure two diseases, diabetes and CHC, with one treatment?