Assessment of insulin secretion in humans under physiologic conditions has been a challenge because of its complex interplay with insulin action and hepatic insulin extraction. The possibility of simultaneously assessing beta cell function, insulin sensitivity and hepatic insulin extraction under physiologic conditions using a simple protocol is appealing since it has the potential to provide novel insights regarding the regulation of fasting and postprandial glucose metabolism in diabetic and non diabetic humans. We review in this perspective data indicating that an OGTT or a meal test is able to accomplish this goal when interpreted with the oral beta cell minimal model. We begin by using the well established intravenous minimal model to highlight how the oral minimal model was developed and how the oral assessment parallels that of IVGTT. We also point out the unique aspects of both approaches in relation to their ability to assess different aspects of the beta cell secretory cascade. We review the ability of the oral model to concurrently measure insulin sensitivity and hepatic insulin extraction thereby enabling it to quantitatively portray the complex relationship between beta cell function, hepatic insulin extraction and insulin action. In addition, data from 204 individuals (54 young and 159 elderly) who underwent both IVGTT and meal tolerance tests are used to illustrate how these different approaches provide complimentary but differing insights regarding the regulation of beta cell function in humans.