The hypothalamic releasing and inhibitory hormones include five major types, which exert stimulating effects on the pituitary gland, leading to the release of five types of corresponding pituitary hormones, of which thyroid-stimulating hormone and adrenocorticotropin (ACTH) in turn stimulate the hormone secretion from thyroid and adrenal cortex, constituting the often referenced hypothalamic-pituitary-thyroid (HPT) axis and hypothalamic-pituitary-adrenal (HPA) axis, respectively, of which the latter will be mainly focused on in this chapter. The HPA axis is one of the most essential pathways among the central nervous system (CNS)‘s influence on the peripheral endocrine functions. The hypothalamic corticotropin-releasing hormone (CRH), together with the arginine vasopressin (AVP), controls the HPA axis’ activity. CRH is the main member among corticotropin-releasing hormone (factor) family peptides (CRF peptides, CRFp) existing and functioning in the brain. Since HPA activation, i.e., CRH (+AVP)-ACTH-cortisol promotion, is a main response of stress, hence the central CRH, as a stress mediator, participates in many physiological and pathological processes. In this chapter, the HPA axis constitution and centrally produced CRH and function will be relatively simply summarized since this book will mainly focus on CRH and the other CRFp’s peripheral existence/origin and their direct peripheral effects (see the following chapters).