Prior findings indicate that trait anhedonia enhances the likelihood of becoming a tobacco smoker, and preliminary evidence suggests that smoking abstinence leads to anhedonic states in some individuals and situations, and nicotine administration reduces anhedonic states. Nevertheless, many vital questions exist concerning relationships between anhedonia and nicotine dependence, including situational and individual difference factors that may moderate the strength of these associations. This chapter provides a critical review of the literature assessing relationships of anhedonia to nicotine dependence and the effects of acute nicotine through the lenses of the Research Domain Criteria's (RDoC) Positive Valence Systems (NIMH, RDoC changes to the matrix (CMAT) workgroup update: proposed positive valence domain revisions. A report by the national advisory mental health council workgroup on changes to the research domain criteria matrix, 2018) and the Situation x Trait Affective Response (STAR) model of nicotine's effects and nicotine dependence (Gilbert, Smoking individual differences, psychopathology, and emotion. Taylor and Francis, Washington, DC, 1995; Gilbert, Hum Psychopharmacol Clin Exp 12:S89-S102, 1997). The effects of nicotine and nicotine withdrawal on subjective, behavioral, and brain indices vary across the three RDoC Positive Valences Systems (Reward Responsiveness, Reward Learning, and Reward Valuation) in a manner that supports the research and potential clinical utility of using RDoC criteria and the STAR model to guide research and clinical innovation. We provide a revision of the STAR model that incorporates the three RDoC Positive Valence Systems with evidence that nicotine's effects on hedonic and affective processes vary as a function of the dominance/salience of (1) situational hedonic and affective cues and task/active coping cues, and (2) state executive functioning level/capacity and state reward sensitivity such that these effects of nicotine are maximal during states of suboptimal cognitive functioning and reward sensitivity, combined with low situational stimulus salience and low task-related cues/demands.