Nutritional decisions are key determinants of health, wellbeing and aging. We want to understand how animals decide what to eat and how these decisions affect the fitness of the animal. To achieve a mechanistic, integrated, whole-animal understanding of nutritional decision-making we work at the interface of behavior, metabolism, microbiome, and physiology in the adult Drosophila melanogaster. I will discuss how the powerful combination of neurogenetics, automated, quantitative behavioral analyses, nutritional and microbial manipulations, and imaging approaches is allowing us to achieve a mechanistic understanding of how neuronal circuits control nutritional decisions to regulate important traits such as aging and reproduction.