Our team at Uppsala University has a broad interest in membrane bound proteins with large focus on GPCRs and solute carriers. We established the GRAFSs classification for the GPCRs in 2003 (Fredriksson et al., 2003) where we showed that the Adhesion-GPCRs are a unique family among GPCRs. We worked with the HUGO nomenclature committee to name several of the human Adhesion-GPCRs. Recently we have mined distant genomes and showed that the Adhesion-GPCRs are among the most ancient evolutionary branches of the GPCRs. These receptors have expanded in numbers in several species and they have rich numbers of N-terminal domains beyond what seen in mammals. We have proposed that the Secretin family is, in evolutionary terms, a child of the Adhesion family. Further studies relate to the functions and evolution of this family as well as opportunities within drug discovery.