Research in the neurosciences offers key concepts that can be applied in residential interventions, by staff and families alike, in “moment in time” interventions as well as in program and system design. This chapter presents an introduction to the application of relevant science related to the neurobiological impact of stress and adversity, and reviews salient principles regarding the brain, body, and stress response. Practical application of the science in interpersonal interactions, sensory and body-based strategies, and residential program design are provided. The authors discuss how the principles provide a scientific underpinning to the practice framework of the Building Bridges Initiative. The voice of lived-experience is incorporated throughout, providing on-the-ground explication of how applying a neurodevelopmental approach can positively impact the experience and outcomes for the youth and families served and supported through residential interventions, and foster residential transformation.