Postmenopausal osteoporosis is the most common form of osteoporosis and results from reduced estrogen levels leading to increased bone turnover with predominant bone resorption. Besides osteoclasts, additional cells including immune cells may contribute to bone loss due to estrogen deficiency. In particular, T and B cells have been shown to drive ovariectomy-induced bone loss in mice by producing pro-inflammatory cytokines such as TNF, IL-6, IL-7, and RANKL. Thus, lymphocytes may not only directly influence osteoclastogenesis, but also indirectly modulate their action via increasing RANKL expression in osteogenic cells. Besides stimulating osteoclasts, T cells can also alter osteoblast behavior. In our ongoing research we show that also in conditions of estrogen deficiency, T cells become activated to produce large amounts of Dickkopf-1 (Dkk1), a potent inhibitor of Wnt signaling. T cell-derived Dkk1 inhibits osteoblastogenesis and stimulates osteoclastogenesis, thereby, contributing to physiological bone remodeling and to the pathogenesis of estrogen deficiency-induced bone loss. Taken together, T cells are important mediators of bone remodeling in health and disease.