The corticotropin-releasing hormone (factor) family peptides (CRFp), including corticotropin-releasing hormone (CRH) and urocortins (UCNs, UCN1–3), function through their two distinct receptors (CRFr), CRF1 and CRF2 (See Chaps. 2 and 3 ). Since the discovery of CRFp in modulating cardiovascular function, more and more researches have been done to elucidate their existence and roles in vascular and cardiac tissues, and clinical trials have been carried out making some of CRFp as novel promising cardiovascular markers in various cardiovascular diseases (CVD). This chapter will focus on the roles of CRFp-CRFr signaling in maintaining normal physiological function of endothelial cells and cardiac myocytes and thus in protecting the health of vasculatures and hearts. Additionally, the possible harmful effects of CRF system on cardiovascular system are also discussed.