Empirical investigations of resilience over the past 30 years have examined a wide range of psychosocial correlates of, and contributors to, this phenomenon. Thus far, theoretical treatments of resilience have focused almost exclusively on psychosocial levels of analysis to derive explanatory models. However, there have been no formal discussions of either theory or research that have examined the biological contributors to, or correlates of, competent functioning despite the experience of adversity. This paper seeks to fill this gap and sets forth a preliminary theoretical framework and outline of empirical strategies for studying the biological underpinnings of resilience. The initial sections of the paper discuss the particular suitability of a transactional organizational theoretical perspective as a conceptual foundation for including a biological level of analysis within the extant theoretical framework of resilience. Subsequently, other important theoretical considerations for the inclusion of a biological perspective on resilience are discussed, including the avoidance of an approach that would reduce resilience to merely a biological process, the application of the constructs of multifinality and equifinality to a biological perspective on resilience, as well as a general discussion of the potential for utilization of brain imaging and other technologies in the study of resilience. The possible relation between the mechanisms of neural plasticity and resilience are examined in some detail, with specific suggestions concerning research questions needed to examine this association. Sections of the paper discuss the likely relation of several areas of brain and biological functioning with resilience, including emotion, cognition, neuroendocrine and immune functioning, and genetics. The paper concludes with a discussion of the implications of a biological perspective on resilience for preventive interventions.