Catecholamines such as norepinephrine (NE) and dopamine mediate a variety of the central nervous system functions, including cognition, memory processing, emotion, motor control, and endocrine modulation. Formaldehyde is closely related to functions of catecholamine neurotransmitters, because (1) formaldehyde is able to react with the alpha-amine group of catecholamines directly and inactivate the transmitter’s function; (2) as a methyl group donor, formaldehyde participates in catecholamine metabolism and 3-O-methylation occurs on catecholamines to be inverted to inactive 3-O-methyl-metabolites in the presence of catechol-O-methyl transferase (COMT) through formaldehyde cycle; (3) also as a methyl group donor, formaldehyde cycle is involved in the conversion of norepinephrine to epinephrine catalyzed by phentolamine N-methyltransferase. Furthermore, aging is associated with formaldehyde accumulation and norepinephrine deficiency in the hippocampus. It is reasonable that formaldehyde accumulation induces hippocampal norepinephrine deficiency, which in turn leads to memory decline during the aging process. Scavenging formaldehyde from or supplying norepinephrine to the hippocampus can rescue memory deficits in aged rats. This chapter focuses on the relationship between formaldehyde and the catecholamine neurotransmitter in the synthesis, function, and neurodegenerative disease, especially age-related cognitive impairment.