Inflammatory bone loss is observed in a number of disorders including rheumatoid arthritis (RA), osteoporosis and periodontal disease. Lymphocytes are key components in the onset and exacerbation of autoimmune diseases and the cytokines produced by these cells have a powerful impact on disease progression. Many cytokines implicated in inflammation impact upon osteoclast (OCL) differentiation and function either directly or indirectly by modulating the relative expression of RANKL and OPG. This review highlights the contribution of lymphocyte-derived cytokines to the bone loss observed in RA and other autoimmune disorders. A greater understanding of the cytokines involved in these disorders will ultimately lead to the identification of novel therapeutic strategies for the prevention of bone loss in these diseases.