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The evolution of the relaxin-like peptide family has long been controversial; points of contention include the existence of an invertebrate relaxin and the absence of a ruminant relaxin. Presented here is the first complete evolutionary analysis of the relaxin-like peptides and their two distinct receptor types. The recent explosion of genomic data provides an excellent resource to study the evolution of gene families and their co-evolution with interacting proteins. The analyses discussed here were able to identify a novel receptor, provide insight into the physiological importance of various interactions between peptides and receptors and clarify the evolution of a clinically relevant family of peptide hormones. The relaxin-like peptide system provides a fascinating insight into the evolution of gene families and hormone-receptor systems as well as highlighting the power of evolutionary analyses of genomic data to study biological systems.