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We reflect upon the histories of the behavioral science and the neuroscience of motivation, taking note of how these increasingly consilient disciplines inform each other. This volume’s chapters illustrate how the field has moved beyond the study of immediate external rewards to the examination of neural mechanisms underlying varied motivational and appetitive states. Exemplifying this trend, we focus on emerging knowledge about intrinsic motivation, linking it with research on both the play and exploratory behaviors of nonhuman animals. We also speculate about large-scale brain networks related to salience processing as a possibly unique component of human intrinsic motivation. We further review emerging studies on neural correlates of basic psychological needs during decision making that are beginning to shine light on the integrative processes that support autonomous functioning. As with the contributions in this volume, such research reflects the increasing iteration between mechanistic studies and contemporary psychological models of human motivation.