NADPH is a ubiquitous electron donor that serves not only biosynthetic pathways but is also the primary source of reducing equivalents necessary for maintaining and regenerating cellular detoxification and antioxidative defense mechanisms. Additionally, it serves as a substrate for NADPH oxidases, which generate reactive oxygen species, further broadening its range of functions. In contrast, NADP+ has acquired signaling functions, potentially impacting crucial cellular processes through its conversion into second messengers in Ca2+ signaling. NADPH-producing and -consuming pathways have important physiological impacts and show potential for the prevention and treatment of metabolic disorders. In this chapter, we will first outline the various known physiological roles and regulation of NADPH. Furthermore, we will emphasize on the changes in the levels of NADPH with age.