Corticotropin-releasing hormone (factor) family peptides (CRF peptides, CRFp) act in both the brain and the periphery to coordinate the overall body response to stress. The involvement of the CRF system (including CRFp, CRF receptors (CRFr), and CRF binding protein (CRF-BP)) in a variety of both central and peripheral disease states has stimulated great interest in this system as a potential site of therapeutic intervention [1]. CRFr belong to class B1 of the super-family of G protein-coupled receptors (GPCRs) [2, 3]. CRFr are classified into two subtypes, CRF1 and CRF2. Both receptors are positively coupled to adenylyl cyclase (AC) but they have a distinct pharmacological feature [4]. As described in Chap. 2 , mammalian CRFp include four members, corticotropin releasing hormone (CRH), Urocortin (UCN1), UCN2, and UCN3. These CRFp mediate the actions through the GPCRs, with CRH selectively on CRF1, UCN1 on both CRF1 and CRF2, and UCN2,3 selectively on CRF2 [5–7]. The cloning of multiple CRFr subtypes has precipitated a new era in CRF system research that has allowed precise molecular, pharmacological, and anatomical examination of mammalian CRFr [8]. This chapter will mainly focus on the basic features of CRFr while their distribution and functions in different peripheral systems will be summarized together with the ligands (CRFp) in the subsequent chapters (Chaps. 4 , 5 , 6 , 7 , and 8 ).