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Work design has largely overlooked cognitive–emotional interactions in understanding employee motivation and satisfaction. My aim in this chapter is to develop a conceptual model that integrates what we know about these interactions from research on emotions and neuroscience with traditional and emergent work design perspectives. I propose that striving for universal goals influences how a person responds to the work characteristics, such that an event that is personally relevant or “self-referential” will elicit an emotional reaction that must be regulated for optimal performance, job satisfaction, and well-being. A Self-Referential Emotion Regulatory Model (SERM) of work design is presented.