Many approaches may be taken in the assessment of insulin sensitivity in humans. The euglycemic hyperinsulinemic glucose clamp and measurement of steady-state plasma glucose are direct but time- and resource-intensive approaches. Alternative approaches, including calculations based on fasting plasma insulin and glucose levels or analyses of glucose and insulin levels after intravenous or oral glucose administration, are useful but provide only modest correlation with the primary analyses. Surrogate measures of insulin sensitivity may be found in body mass index, waist circumference, or serum triglyceride or C-reactive peptide determination. New, innovative isotopic approaches now being developed offer the potential to characterize whole-body glucose metabolism in a fashion that may eventually allow routine clinical testing of insulin sensitivity.