Consumption of ethanol during the course of cocaine binges is common, with an estimated prevalence well in excess of 50%. Cocaine abusers indicate that coingestion of ethanol may enhance and/or prolong the euphoria and reduce unpleasant side effects that may follow. Cocaethylene, an active homologue/metabolite that arises through transesterification of cocaine following coconsumption of cocaine and alcohol, shares many neurochemical and behavioral properties with cocaine and reaches significant blood concentrations. However, cocaine and cocaethylene also appear to differ in some respects, including the relative potency of their actions on the dopamine and serotonin transporters. Information obtained from animal and human studies of the neurochemical and behavioral properties of cocaethylene and of cocaine-ethanol interactions is reviewed, and the possible implications with respect to the mechanisms and consequences of combined cocaine and ethanol abuse are described.