Succinate functions not only as an energy source and building block but also as an extracellular messenger, signaling via the G-protein coupled receptor (GPCR) GPR91. Metabolic stress conditions cause the levels of succinate to rise, enabling activation of GPR91. The physiological role of GPR91 on whole body metabolism, however, is still unclear. Trauelsen and colleagues developed drug-like non-metabolite GPR91 agonists as potential pharmacological tools by using a receptor structure-based approach. The compounds they identified should make it possible to study effects of selective GPR91 activation in an in vivo setting after oral administration.