Nicotinamide coenzyme II NADPH levels decline with age, primarily due to the age-dependent loss of its synthetic precursor NAD+. Dysfunction in the electron transport chain (ETC) during aging also diminishes the proton motive force across the inner mitochondrial membrane, thereby reducing the ability of mitochondrial nicotinamide nucleotide transhydrogenase (NNT)-mediated NADP+ and NADH to synthesize NADPH and NAD+. NADP+/NADPH is the most important redox pair in combating cellular oxidation induced by aging. The oxidation rate and energy of the NADP+/NADPH redox pair decline with age. Aging leads to oxidative stress-mediated cellular dysfunction and depletion of endogenous antioxidants. NADPH can protect cells from oxidative stress, thereby postpone tissue and organismal aging. Studies on various organisms like Drosophila, yeast, nematodes, and mammals have demonstrated that NADPH levels influence lifespan. However, elevated NADPH levels may stimulate NADPH oxidase (NOX)-induced generation of reactive oxygen species (ROS), consequently hastening the aging process. This chapter will discuss the role of NADPH in the aging process and possible benefits of NADPH in aging.