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Importantly, resilience is not merely the inverse of vulnerability, but a process that can be investigated in its own. In this review, we clarify this concept of resilience and its distinction from tolerance and resistance, and situate human lung resilience within a cross-organ and cross-species framework. We also critically assess the hypothesis that evolutionary processes may have influenced human resilience to smoke exposure. Finally, we advocate for rigorous clinical phenotyping and mechanistic approaches to dissect the interplay between genetics, physiology, and evolution. 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