The finding of corticotropin-releasing hormone (CRH) signaling further promotes the study of biological stress since the stress concept pioneering by Selye [1, 2]. After the identification of central CRH signaling pathways by Vale group [3–5], all corticotropin-releasing hormone (factor) family peptides (CRF peptides, CRFp)‘s peripheral presence and functions have been widely studied. The discovery of peripheral CRH is interesting and preludes the wide investigations on all CRFp outside the brain. It is found by Hargreaves et al. that pituitary corticotroph secretion of β-endorphin can be either caused by hypothalamic CRH or by a tissue factor from the periphery in response to stressors. Rats’ inflamed tissue is observed to release a factor, evoking pituitary secretion of β-endorphin, which is independent of the afferent input with the inability of the hindlimb denervation to block the effect. Also, the subcutaneous perfusates stimulate β-endorphin release in cultured pituitary cells [6]. By analyzing human tissues, it is found that CRH outside the brain is identical to hypothalamic CRH [7]. Afterward, the existence and role of peripheral CRFp have attracted wide attention [8]. Mammalian CRFp include four members, CRH, urocortin (UCN1), UCN2, and UCN3, signaling through two distinct CRF receptors (CRFr) belonging to B1 G protein-coupled receptor (GPCR) types, CRF1 and/or CRF2, to modulate a range of peripheral activities [8–12]. This chapter mainly focuses on the structures of CRFp and their overall distributions in important systems including the digestive, cardiovascular, immune/inflammatory, and reproductive system.