Many acute and chronic lung diseases could benefit from improved regeneration therapy. In development and throughout life, genetically encoded exposure memory systems allow environmental exposures, diet, and infectious agents to direct subsequent phenotypic adaptation and responses. The impact of such memory systems on lung regeneration is currently unknown. This article provides a brief overview of advances in redox biology and medicine as a framework for elucidating exposure memory and delineating spatiotemporal responses in lung regeneration. New imaging and omics methods enable precise definition to advance knowledge of development and the cumulative changes in lung biochemistry, structure, and cell populations occurring from prior and ongoing exposures. Importantly, conditioning steps may be needed to reverse exposure memory and enable effective regeneration. Thus, to complement developmental biology and regenerative medicine, research programs are needed to gain systematic knowledge of how lifelong exposures impact lung biology and support transition of lung regeneration from hypothetical to practical medicine.