Neuroscientific tools and approaches such as neuroimaging, measures of neuroendocrine and psychoneuroimmune activity, and peripheral physiology are increasingly used in clinical science and health psychology research. We define translational neuroscience (TN) as a systematic, theory-driven approach that aims to develop and leverage basic and clinical neuroscientific knowledge to aid the development and optimization of clinical and public health interventions. There is considerable potential across basic and clinical science fields for this approach to provide insights into mental and physical health pathology that had previously been inaccessible. For example, TN might hold the potential to enhance diagnostic specificity, better recognize increased vulnerability in at-risk populations, and augment intervention efficacy. Despite this potential, there has been limited consideration of the advantages and limitations of such an approach. In this article, we articulate extant challenges in defining TN and propose a unifying conceptualization. We illustrate how TN can inform the application of neuroscientific tools to realistically guide clinical research and inform intervention design. We outline specific leverage points of the TN approach and barriers to progress. Ten principles of TN are presented to guide and shape the emerging field. We close by articulating ongoing issues facing TN research. (PsycINFO Database Record (c) 2019 APA, all rights reserved).