Cytokines are secreted by several cell types in the bone microenvironment. These peptides act on bone cells by a paracrine or autocrine mechanism and play an important role, although not completely clarified, in the regulation of bone remodeling. Postmenopausal osteoporosis could be due to a local overproduction of some osteoclast-stimulating cytokines in response to estrogen deficiency. During chronic inflammatory joint diseases, such as rheumatoid arthritis, synovial cells produce large amounts of cytokines leading to increased local bone resorption and juxta-articular bone destructions. The local action of cytokines is also involved for interactions between tumoral cells and bone cells. These are secreted by the tumoral (metastatic or hemopoietic) cells, bone marrow cells, bone cells, or even could be released from the bone matrix during bone resorption. Recent progress in our knowledge in the field of cytokines have improved the understanding of the pathogenesis of these diseases and let hope future promising developments for more specific treatments.