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The evolutionary significance of neurochemical events in the brain has received minimal attention in the field of addiction research. Likewise, the general failure of neuroscientists to postulate how basic brain circuits might mediate emotional urges has retarded the development of scientific perspectives that could inform new inquiries into the underlying dynamics and treatment of addictions. In this paper, we revisit the argument that prototypically abused substances activate or alter specific emotional brain systems that were evolutionarily designed to signal potential increments or decrements in fitness. We then discuss two distinct emotional systems (reward seeking and separation distress) which may track different types of potential changes in fitness. Based on this evolutionarily inspired approach, we illustrate how a mammalian model of emotion (i.e. rodent ultrasonic vocalizations) may enable scientists to predict drug-related phenomena such as abuse potential, anatomical location of mediating neural substrates, and the psychological impact of withdrawal. We conclude by discussing some therapeutic and social implications of examining drug addiction processes with multiple emotional brain systems in mind.