This review presents a novel conceptualization of addiction, integrating the concepts of interoception (i.e., the CNS representation of visceral feelings) and alliesthesia (i.e., that rewarding properties of stimuli are dependent on the internal state of the individual) with existing theories. It is argued that the body state, as defined by the integration of interoceptive information, is a crucial arbiter of the risk for initiation of and transition to compulsive use of addictive compounds. Overall, individuals at risk for drug dependence are characterized by an altered internal bodily state that leads to a change in hedonic and incentive motivational properties of addictive drugs. Specifically, drug dependent individuals experience alliesthesia of interoceptive processing, leading to increased incentive motivational properties of the drug over time and thereby increasing the probability of subsequent use. This extension of previous theories of addiction to include interoception and alliesthesia is based upon a clearly delineated set of neural substrates mediating interoception, key elements of which also recently have been implicated in drug addiction. The model thereby provides new potential targets for interventions that are aimed at changing the internal state that puts the individual at risk for continued substance use.