About half of all murders are committed in Western industrialized countries by subjects under the influence of alcohol. Chronic alcohol use also increases the rate of violent attacks. These findings appear to be due to an interaction between acute and chronic environmental effects (acute alcohol consumption and chronic social isolation stress) on the one hand and limbic processing of aversive stimuli modulated by neurotransmitter systems such as dopamine and serotonin on the other. Animal experiments showed that early social isolation stress can induce serotonin dysfunction and appears to predispose individuals towards increased threat perception. Studies in humans revealed that depending on serotonergic neurotransmission and serotonin transporter genotype, some individuals are prone to show elevated functional activation elicited by aversive and threatening cues. Previous experience with alcohol-related aggression seems to further predispose an individual towards a “fight vs. flight” reaction when confronted with perceived threat during alcohol intake. Together, these findings point to complex gene-environment interactions and a specific role of social isolation stress in the development of alcohol-related aggression.