In this issue of Molecular Metabolism, Dushay et al. report new results demonstrating fructose ingestion in humans acutely and robustly raises circulating levels of fibroblast growth factor 21 (FGF21) [1], a recently discovered hormone that has been proposed to have beneficial effects on metabolic health, including reduction of body weight and improvements of glucose and lipid metabolism [2]. People suffering from the metabolic syndrome have higher baseline circulating FGF21 levels and exhibit a larger increase of plasma FGF21 concentrations following an oral fructose load.