As described in the previous chapters, mammals have four mature corticotropin-releasing hormone (factor) family peptides (CRF peptides, CRFp), namely, corticotropin-releasing hormone (CRH), urocortin (UCN1), UCN2, and UCN3, which are the evolutionary results from an ancestral peptide precursor early in metazoan ancestry [1, 2]. These neuropeptides may induce intricating physiological responses by exerting their actions on two distinct types of CRF receptors (CRFr), CRF1 and CRF2, which belong to the class B1 family of G-protein-coupled receptors (GPCRs) (Chap. 3 ) [3]. Among non-mammals, CRFp are relatively more investigated in fish and insects, representing vertebrates and invertebrates, respectively. Vertebrates’ CRFp consist of four distinct paralogous lineages found on separate chromosomes, which are CRH, urotensin-I (UTI)/UCN1/sauvagine (Svg), UCN2, and UCN3, the former two representing a gene duplication from one lineage, while the latter two being results from the other similar lineage [1, 4]. Invertebrates’ CRFp are relatively characterized well in insects, which evolve in ancestral species before the Precambrian times. And diuretic hormones (DHs) in insects are found to be highly similar to CRFp [4–6]. Collectively, non-mammal CRFp originate from a gene duplication of a single ancestral CRH-like peptide conserved from a horizontal gene transfer event, having some difference from mammal CRFp [1]. This chapter will focus on the distribution and main function of non-mammal CRFp.