We have two intentions by means of this review: to summarize the contributions of oxidative stress, either pulmonary lesions related ROS accumulation and metabolic/endocrine disorders-related ROS accumulation, to pneumonia susceptibility, and to discuss how AMPK-Nrf2 signaling contributes to maintain the metabolic and endocrine homeostasis that is the fundamental status of the body to resist pulmonary infection, to alleviate pulmonary lesions, and to prevent pneumonia. The gene discussed is NFE2L2; the disease is pneumonia.