Sex/gender difference exists in the physiology of multiple organs. Recent epidemiological reports suggest the influence of sex-steroids in modulating a wide variety of disease conditions. Sex-based discrepancies have been reported in pulmonary physiology and various chronic inflammatory responses associated with lung diseases like asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, and rare lung diseases. Notably, emerging clinical evidence suggests that several respiratory diseases affect women to a greater degree, with increased severity and prevalence than men. Although sex-specific differences in various lung diseases are evident, such differences are inherent to sex-steroids, which are major biological variables in men and women who play a central role to control these differences. The focus of this chapter is to comprehend the sex-steroid biology in inflammatory lung diseases and to understand the mechanistic role of sex-steroids signaling in regulating these diseases. Exploring the roles of sex-steroid signaling in the regulation of lung diseases and inflammation is crucial for the development of novel and effective therapy. Overall, we will illustrate the importance of differential sex-steroid signaling in lung diseases and their possible clinical implications for the development of complementary and alternative medicine to treat lung diseases.