This chapter concentrates on three areas of model development. First, it presents data showing how differential impacts to specific neural regulatory systems are associated with variations by the type of early life stress (ELS) experienced. Second, the chapter describes how studies of the severity of ELS are providing a new basis for understanding trajectories towards risk versus resilience among foster children and other populations who experience ELS. Third, it also describes a growing body of evidence documenting the plasticity of these neural systems in response to psychosocial, family-based therapeutic interventions. The chapter focuses on the neurobiological systems involved in the reaction and the regulation of physiological responses to stressors. Much work remains to be done across the spectrum of risk and resilience following ELS in order to improve the identification of individuals in need of services and to specify the techniques most likely to improve outcomes.