The National Institutes of Health (NIH) have recently gathered internal and external input towards a shared understanding of resilience in the wide context of human health and the biomedical sciences that would help accelerate advances in human health and its maintenance. This shared view is that resilience refers in general to a system's capacity to recover, grow, adapt, or resist perturbation from a challenge or stressor. Over time, a system's response to a challenge might show varied degrees of reactions that likely fluctuate in response to the type of challenge (internal and/or external), severity of the challenge, the length of time exposed to the challenge, other external factors and/or biological factors (innate and/or external). We have embarked on this special issue as an opportunity to explore commonalities amongst viewpoints on the science of resilience covered by the various NIH Institutes, Centers, and Offices (ICOs) with respect to the characterization of various systems, stressors, outcomes measures and metrics, and interventions and/or protective factors that are shared within each domain and across multiple domains. Here, resilience is characterized broadly by four areas of scientific study: molecular/cellular, physiologic, psychosocial and spiritual, and environmental/community resilience. Each area or domain provides general frameworks for designing studies that may help advance the science of resilience within the context of health maintenance. This special issue will also acknowledge the remaining gaps that impede advancement of the science of resilience and offer considerations for potential next steps towards addressing the research gaps.