The primary function of SGLT1 is to transport glucose across the brush border membrane of the human intestine. The clearest evidence for this is that subjects with mutations in SGLT1 are unable to absorb significant amounts of glucose. For example, adult subjects with Glucose-Galactose-Malabsorption caused by SGLT1 mutations are unable to absorb glucose as judged by oral tolerance and hydrogen breath tests (Wright et al. 2003). Members of the SLC5 gene family including SGLT1 (Wright & Turk, 2004) have other important functions as Na-uniporters, water and urea channels, water cotransporters, and glucosensors (Wright et al 2004). For example, SGLT1 behaves as a water channel and pump and so the 250,000 copies in the intestinal brush border of each enterocyte can account for the absorption of up to 6 liters of fluid a day across the brush border (Loo et al. 2001). Human SGLT3 is not a Na/glucose cotransporter but a glucosensor (Wright et al 2004). In response to an increase in glucose concentration this protein transports Na into the cell and this causes a depolarization of the membrane potential. In those cells where SGLT3 is expressed, cholinergic neurons in the enteric nervous system and neuroendocrine cells, this depolarization results in an increase in frequency of action potentials and, at least in neuroendocrine cells, an increase in peptide secretion. Thus SGLT3 in the gut may play an important role in the response of the GI tract to a meal. SGLT genes are expressed brain, heart, lung and muscle and so our challenge is to determine the physiological significance of their diverse functions in these organs and tissues. Careful study of human subjects with mutations in SGLT genes may provide some clues to resolving this challenge.