Osteoporosis, a chronic bone disease, alters both the microstructure and macrostructure of bones, endangering bone strength and increasing the susceptibility to fragility fractures. Its consequences on the aging population raise important sociological, healthcare, and economic issues. The relationship between the immune system and osteoporosis can be understood by carefully examining a wide range of immune cells, related cytokines, and their functions. Long-term inflammation, immune cell production of RANKL, and autoimmune illnesses like systemic lupus erythematosus and rheumatoid arthritis all affect bone loss. An overview of the cycle of bone remodeling and the pathophysiology of osteoporosis are covered in this chapter. Important features of osteoporosis for diagnostic purposes are covered, including the formation and resorption markers, potential immunological markers for osteoporosis diagnosis, and new bone metabolic biomarkers. This chapter focuses solely on the roles of innate and adaptive immune cells. It also highlights novel therapeutic strategies that target specific immune pathways and show promise in the management of these challenging bone disorders. As research advances, these findings may pave the way for more specialized and efficient treatments, ultimately enhancing the quality of life for osteoporosis patients.