Recent pharmacological and genetic studies have dramatically expanded the list of neurotransmitters, hormones, cytokines, enzymes, growth factors, and signaling molecules that influence aggression. In spite of this expansion, serotonin (5-HT) remains the primary molecular determinant of inter-male aggression, whereas other molecules appear to act indirectly through 5-HT signaling. We review evidence of interactions among these molecules and aggressive behavior. Slight modulations in 5-HT levels, turnover, and metabolism, or in receptor subtype activation, density, and binding affinity affect aggression. Activation of specific 5-HT receptors evokes distinct, but highly interacting, second messenger systems and multiple effectors. Understanding the interactions between 5-HT receptor subtypes should lead to novel insights into the molecular mechanisms of aggression.