Resilience has been conceptualized as a dynamic developmental process encompassing the attainment of positive adaptation within the context of significant threat, severe adversity, or trauma. Until the past decade, the empirical study of resilience predominantly focused on behavioral and psychosocial correlates of, and contributors to, the phenomenon and did not examine neurobiological or genetic correlates of and contributors to resilience. Technological advances in molecular genetics and neuroimaging, and in measuring other biological aspects of behavior, have made it more feasible to begin to conduct research on pathways to resilient functioning from a multilevel perspective. Child maltreatment constitutes a profound immersion in severe stress that challenges and frequently impairs development across diverse domains of biological and psychological functioning. Research on the determinants of resilience in maltreated children is presented as an illustration of empirical work that is moving from single-level to multilevel investigations of competent functioning in the face of adversity and trauma. These include studies of personality, neural, neuroendocrine, and molecular genetic contributors to resilient adaptation. Analogous to neural plasticity that takes place in response to brain injury, it is conjectured that it may be possible to conceptualize resilience as the ability of individuals to recover functioning after exposure to extreme stress. Multilevel randomized control prevention and intervention trials have substantial potential for facilitating the promotion of resilient functioning in diverse high-risk populations that have experienced significant adversity. Determining the multiple levels at which change is engendered through randomized control trials will provide insight into the mechanisms of change, the extent to which neural plasticity may be promoted, and the interrelations between biological and psychological processes in the development of maladaptation, psychopathology, and resilience.