Recent theories have posited specific ethanol-binding sites on several proteins that may act directly or indirectly to produce a biological effect (Figure 1). To understand how ethanol affects the brain and behavior using a bottom-up approach, it is important to first distinguish between the direct and indirect effects of ethanol. To that end, the following criteria have been proposed to classify direct ethanol targets (Harris et al., 2008; Trudell et al., 2014):