Lung diseases encompass a variety of different disease entities, which differ in etiology, acuity, underlying pathologies, and mortality but represent a significant public health burden to our society. Currently, more than 25 million people in the United States have been diagnosed with asthma and approximately 14.8 million adults have chronic obstructive pulmonary disease (COPD). Fibroblast growth factor 23 (FGF23) has been shown to be associated with systemic inflammation and increased mortality in chronic kidney disease. It has been shown that serum FGF23 levels are also increased in individuals with COPD and cystic fibrosis, two diseases that are associated with airway inflammation. Furthermore, α-klotho, the coreceptor for FGF23, has been implicated in occupational lung disease and pulmonary vascular disease. This chapter will present current literature discussing the contribution of FGF23 and α-klotho signaling in the pathogenesis of acute and chronic lung disease. We will also discuss modulation of FGF23 signaling as future treatment options for pulmonary disease.