Abstract. Alcohol dependence is a major public health problem. Studies have shown that a person dependent on alcohol often coabuses other substances, such as cocaine. Cocaine is a powerful stimulant whereas ethanol is generally considered to be a depressant, with some stimulating properties. The subjective effects of these two substances in a dependent individual may often appear to be more similar than they are different. Animals also self-administer both substances. Basically, although both substances have anesthetic properties and both act to functionally increase catecholaminergic function, especially that of dopamine, there are some differences in their actions. Both alcohol and cocaine have various effects on several neurotransmitters and systems, which ultimately interact to produce the feeling of well-being avidly sought by many individuals today. This drive often eventually produces a dependence which has associated social and medical consequences. It seems likely that the neurochemical changes that ensue following abuse of these substances underlie the phenomena of dependence, tolerance, and subsequent withdrawal. The apparent similarities and differences between these two substances will be reviewed in this chapter.