The mammalian proglucagon gene encodes three related sequences, glucagon and the glucagon-like peptides 1 and 2 (GLP-1 and GLP-2), each of which has an essential role in metabolism. A family of closely related receptors mediates the physiological actions of these hormones. Intriguingly, GLP-1 has opposite functions in mammals and fish. In mammals, secretion of GLP-1 results in a reduction in blood sugar levels, whereas in fish it causes an increase. The recent release of draft genome sequences of diverse vertebrates has made it possible to examine the evolution of the receptors for these peptide hormones. Phylogenetic analysis of sequences of receptors for proglucagon-encoded hormones suggests a potential explanation for the change in function of GLP-1 between fish and mammals. I suggest that in fish, GLP-1 lost the ability to act on insulin-secreting cells and was recruited as a ligand for a duplicated glucagon receptor, resulting in a physiological action similar to that of glucagon.