Osteoporosis is a degenerative, multifactorial osteometabolic disease characterized by a reduction in bone mineral density and deterioration of tissue microarchitecture. Of the various systemic and local factors involved in the etiopathogenesis of the disease, the association between components of the immune system and the genetic background has been shown to be key in maintaining bone tissue homeostasis. As a multifactorial disease, it is essential that its main causes are identified early, thus preventing the progression of the disease. Cytokines are recognized as participating in this homeostasis, acting to alter tissue resorption and controlling the proliferation of bone cells. Polymorphisms in the genes of these cytokines, such as SNPs, can interfere with their structures and expression levels, modifying the biological mechanisms in which they are involved. Therefore, the aim of this book was to verify the role of IFN-Gamma in this process, by analyzing the rs2069705 polymorphism, expression levels and in vitro activity of the protein. In this way, we hope to contribute to filling the gaps still present in the field of Osteoimmunology in the study of Osteoporosis.