Coenzyme II exists in the body as oxidized NADP+ and reduced NADPH, serving as a crucial cofactor and antioxidant factor in cellular processes. The primary biological functions of NADPH encompass maintaining the cellular antioxidant defense system, acting as a coenzyme for the glutathione system, catalase, and superoxide dismutase; participating in fatty acid, steroid, and DNA synthesis by functioning as an electron donor; contributing to energy metabolism; and regulating the circadian rhythm. Additionally, NADPH can serve as a substrate for NOX family of proteins (NOX1-7), leading to the generation of reactive oxygen species (ROS) that play pivotal roles in various physiological and pathological processes. In inflammatory pathways involving neutrophils and phagocytes, NADPH acts as a substrate for NOX enzymes to promote pathogen killing through superoxide production. Moreover, NADPH can generate reactive nitrogen species (RNS) via nitric oxide synthase (NOS), thus significantly contributing to protein nitration stress. Recent studies have also demonstrated that NADPH can bind certain signaling molecules and modulate their functions. This chapter provides an overview of the physiological functions of NADPH.