Coenzyme I is primarily found in the cytoplasm as NAD+, and coenzyme II is mostly found in the mitochondria as NADPH. As NAD(H) and NADP(H) have different spatial conformations, they can bind to different enzymes. NADPH is synthesized by various pathways utilizing different enzymes. All the NADP+ dehydrogenases commonly have different cytoplasmic and mitochondrial isozymes for the formation and utilization of the cofactors NAD(H) and NADP(H) at the required site. However, the interconversion of these coenzymes, facilitated by trans-organelle transport mechanisms, holds significant implications for redox signaling, cellular homeostasis, and overall health. This chapter will highlight the biochemical pathways underlying the interconversion of coenzymes I and II, emphasizing the enzymes and regulatory factors/shuttles involved in this dynamic process.