The peptide hormone GDF15 is a potent anorectic factor. Raised circulating levels of GDF15 are seen in a large number of pathological disorders and are associated invariably with adverse clinical outcomes. GDF15 signalling is mediated through GFRAL receptor in the hindbrain. A greater understanding of the mechanisms that drive expression of GDF15 within different tissues has led to the GDF15-GFRAL axis being considered a route through which somatic distress is signalled to the brain. We highlight key recent insights into the role of GDF15 in appetitive behaviour and reflect on the therapeutic potential of the system for disorders of energy balance.