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Insulin resistance, HIV, antiviral drugs and hepatitis C virus (HCV) infection contribute to a complex interaction involving the metabolic syndrome. The objective of this review was to explore the meaning of insulin resistance in HIV–HCV-coinfected patients and how it may impact on sustained virological response (SVR) and disease progression.In the HIV/HCV coinfection setting, insulin resistance seems to be associated with a reduction in rapid virological response and SVR to pegylated interferon and ribavirin, both in naive and treatment experienced patients. A recent meta-analysis demonstrated insulin resistance impairs SVR rate with an odds ratio 0.47 (95% confidence interval 0.31–0.71). However, many confounding factors may promote contradictory results. Prevalence of insulin resistance depends on surrogate markers of insulin resistance and the threshold for defining impaired insulin sensitivity. For example, homeostasis model for the assessment of insulin resistance may be influenced by both methods of insulin measurement and interpretation. Insulin sensitizers, lifestyle changes and improvement in the use of protease inhibitors should be evaluated in the management of coinfected patients.Insulin resistance is common finding in patients with HIV/HCV coinfection, with wide clinical consequences including progression of hepatic fibrosis and reduction in the response to antiviral treatment. Our understanding of this relationship continues to improve. More prospective studies are required to improve future management.