Insights from over a decade leading the Neuroscience component of the longitudinal, multi-project Midlife in the United States National Study of Health and Wellbeing (MIDUS) will be shared from the perspective of an affective neuroscientist with a research focus on the emotional determinants of health, wellbeing, and brain aging. MIDUS offers much opportunity to identify the linkages between affective style, health, wellbeing, and brain aging, as well as the sociodemographic, psychosocial, environmental, and lifestyle factors that moderate those relationships. Brief highlights of past and current findings from the MIDUS Neuroscience Project will be described as examples of the types of questions that can be asked of the data. The new opportunities provided by the expanded data collected in the current follow-ups of the MIDUS samples will also be discussed, as well as how these data may add to our knowledge of how to promote and retain emotional wellbeing and brain health throughout the lifespan.