Nudix hydrolases constitute a large family of proteins distributed in all living organisms and hydrolyze a wide variety of substrates, including coenzymes of niacin, pantothenic acid, and flavin, that contain a nucleoside diphosphate linked to some other moiety, X. There is increasing evidence of the regulatory roles for plant Nudix hydrolases in various physiological processes such as stress responses and the metabolism of various molecules. Arabidopsis thaliana has 28 Nudix hydrolases (AtNUDX1-27, and AtDCP2) located in the cytosol, mitochondria, and chloroplasts. Among them, AtNUDX2, 6, and 7 play regulatory roles in biotic and abiotic stress responses through the precise modulation of the intracellular levels of ADP-ribose and/or NAD(P)H. On the other hand, AtNUDX11 and 15 affect CoA biosynthesis and various CoA-related pathways in the cytosol and mitochondria. Flavin homeostasis is achieved by the regulation of the balance of FAD and FMN by AtNUDX23 in chloroplasts. These findings suggest that plants develop degradation pathways for vitamin coenzymes by Nudix hydrolases essential for their growth and survival.