Resilience science in psychology and related fields emerged from clinical research on risk for psychopathology in the 1970s and matured over the ensuing decades with advances in theory, methods, and knowledge. Definitions and models of resilience shifted to reflect the expanding influence of developmental systems theory and the growing need to integrate knowledge about resilience across levels and disciplines to address multisystem threats. Resilience is defined for scalability and integrative purposes as the capacity of a dynamic system to adapt successfully through multisystem processes to challenges that threaten system function, survival, or development. Striking alignment of resilience factors observed in human systems, ranging from individuals to communities, suggests the possibility of networked, multisystem protective factors that work in concert. Evidence suggests that there may be resilience factors that provide transdiagnostic protection against the effects of adverse childhood experiences on risk for psychopathology. Multisystem studies of resilience offer promising directions for future research and its applications to promote mental health and positive development in children and youth at risk for psychopathology.