A common criticism of the Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 2013) is that its criteria are based more on behavioral descriptions than on underlying biological mechanisms. Increasingly, calls have intensified for a more biologically-based approach to conceptualizing, studying, and treating psychological disorders, as exemplified by the Research Domain Criteria Project (RDoC). Among the most well-studied neurobiological mechanisms is reward processing. Moreover, individual differences in reward sensitivity are related to risk for substance abuse and depression. The current review synthesizes the available preclinical, electrophysiological, and neuroimaging literature on reward processing from a transdiagnostic, multidimensional perspective. Findings are organized with respect to key reward constructs within the Positive Valence Systems domain of the RDoC matrix, including initial responsiveness to reward (physiological 'liking), approach motivation (physiological 'wanting'), and reward learning/habit formation. In the current review, we (a) describe the neural basis of reward, (b) elucidate differences in reward activity in substance abuse and depression, and (c) suggest a framework for integrating these disparate literatures and discuss the utility of shifting focus from diagnosis to process for understanding liability and co-morbidity. Ultimately, we believe that an integrative focus on abnormal reward functioning across the full continuum of clinically heterogeneous samples, rather than within circumscribed diagnostic categories, might actually help to refine the phenotypes and improve the prediction of onset and recovery of these disorders. (C) 2015 Elsevier B.V. All rights reserved.