Methods: We conducted a comprehensive literature search in the PubMed database using the keywords “HIF-1,” “sepsis,” “lung injury,” “metabolic reprogramming,” “immunity,” and “inflammation.” All relevant articles and reviews published since database inception were retrieved and screened to identify studies addressing the role of HIF-1 in the pathophysiological processes of S-ALI. The gene discussed is HIF1A; the disease is Sepsis.