Insulin resistance is one pretty troublesome entity which very commonly aggravates metabolic syndrome. Many methods and indices are available for the estimation of insulin resistance. It is essential to test and validate their reliability before they can be used as an investigation in patients. At present, hyperinsulinemic euglycemic clamp and intravenous glucose tolerance test are the most reliable methods available for estimating insulin resistance and are being used as a reference standard. Some simple methods, from which indices can be derived, have been validated e.g. homeostasis model assessment (HOMA), quantitative insulin sensitivity check index (QUICKI). For the clinical uses HOMA-insulin resistance, QUIKI, and Matsuda are suitable, while HES, McAuley, Belfiore, Cederholm, Avignon and Stumvoll index are suitable for epidemiological/research purposes. With increasing number of these available indices of IR, it may be difficult for clinicians to select the most appropriate index for their studies. This review provides guidelines that must be considered before performing such studies.