At present, there is a good understanding of the negative neurobiological impacts that ethanol has on adolescent and adult brains; the effects of this drug on the aging brain, both normal and pathological, are only now starting to emerge. Biomedical research involving the effects of alcohol on aging is limited; however, studies in human subjects show that older adults perform worse in tests assessing working memory, attention, and cognition as compared to younger adults. The neurobiological basis for these effects in the elderly is largely unknown. In the last 30 years, important molecular targets for ethanol actions in the adolescent and adult brain have been identified. Yet, we know very little about whether these targets are still affected by ethanol in the older brain. The brain structure changes during aging, and the targets and their functional characteristics may also change. Thus, one can expect that ethanol will have distinct effects on the brain of an aged organism. This chapter discusses the available data showing how aging influences critical proteins that affect neuronal excitability, nerve conduction, and synaptic transmission and how aging modifies the sensitivity of these proteins to ethanol. The data show limited information on ethanol’s effects in the aged brains of mice and rats.