Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide, which is characterized by a persistent airflow limitation caused by chronic inflammatory responses to noxious particles or gases. Cigarette smoke and environmental pollutions are major etiological factors for causing COPD. It has been shown that cigarette smoking causes abnormal inflammatory responses, cellular senescence, mitochondrial dysfunction and metabolic dysregulation, suggesting their involvement in the development of COPD. Although the medical care and treatment have advanced, there are no effective therapies to stop or reverse lung destruction in COPD/emphysema. AMP‐activated protein kinase (AMPK) is a serine threonine kinase with α, β, and γ subunits that are highly conserved through evolution. AMPK has been shown to regulate bioenergetics, inflammatory responses, senescence, and metabolism. This review focused on the updated understanding of molecular pathogenesis of COPD, and highlighted the crucial roles of AMPK in lung abnormalities as well as discussed the potential therapeutics of AMPK activators in preventing and halting the progression of COPD. Cigarette smoke as well as other gases and particles cause inflammatory responses, senescence, mitochondrial dysfunction, and metabolic dysregulation, leading to lung destruction and subsequently COPD/emphysema. AMPK is reduced by cigarette smoke and in lungs of COPD patients, and AMPK activators protect against aforementioned cellular processes and pulmonary emphysema.