Over fifty years ago chromium was proposed to have an essential biochemical role in the metabolism of carbohydrates and lipids, and subsequently its status as an essential element was widely accepted. Unfortunately, these studies confused the pharmacological effects of large, supra-nutritional doses of Cr for nutritional effects. Recent research has firmly established that chromium is not an essential or conditionally essential element for mammals but has effects on insulin sensitivity and cholesterol levels only at pharmacologically relevant doses. However, the mechanism of these effects in rodent models of obesity-associated insulin resistance and type 1 and type 2 diabetes at a molecular level has not been elucidated, although a direct effect on insulin signaling cascade is suggested by current data. This research addresses recent studies that demonstrated that chromium is not essential but pharmacologically active through the use of purified rat diets with varying concentrations of chromium. Urinary chromium excretion in response to an insulin challenge is not a biomarker for Cr status, the effect Cr supplementation on tissue metal concentrations and that Cr is not a conditionally essential element for diabetics as increased Cr urinary excretion in diabetics reflects an increase in absorption using Cr51 tracer studies.