Much effort has been directed at studying the orexigenic actions of administered ghrelin and the potential effects of the endogenous ghrelin system on food intake, food reward, body weight, adiposity, and energy expenditure. Although endogenous ghrelin's actions on some of these processes remain ambiguous, its glucoregulatory actions have emerged as well-recognized features during extreme metabolic conditions. The blood glucose-raising actions of ghrelin are beneficial during starvation-like conditions, defending against life-threatening falls in blood glucose, but they are seemingly detrimental in obese states and in certain monogenic forms of diabetes, contributing to hyperglycemia. Also of interest, blood glucose negatively regulates ghrelin secretion. This article reviews the literature suggesting the existence of a blood glucose-ghrelin axis and highlights the factors that mediate the glucoregulatory actions of ghrelin, especially during metabolic extremes such as starvation and diabetes.