Despite over 60 years’ accumulation of data from animal studies indicating that the kidney produces glucose responsive to hormonal and other physiologic and pathologic perturbations, most medical textbooks consider the liver to be the sole source of glucose in humans under most conditions. This view was based on simple (no longer valid) net renal glucose balance calculations. However, recent studies in humans and dogs using more sophisticated techniques (net balance plus isotopic measurements) indicate 1) that the kidney simultaneously produces and uses glucose and that it is a major gluconeogenic organ; 2) that the human kidney contributes significantly to the overall release of glucose into the circulation postabsorptively and under other conditions; and 3) that its release of glucose is under hormonal control and is increased during hypoglycemia and in diabetes.