Many factors such as vitamins, hormones and cytokines, control bone metabolism and remodeling. Cytokines of the interleukin-6 family, by acting on bone cells (i.e. osteoblasts and osteoclasts), have an important role in the bone tissue but they recently appeared as double-edged swords. They sustain bone formation but they can also drive bone loss in various osteolytic pathologies. Similarly, development of bone cancers can be either prevented or enhanced by these cytokines, depending on the cell type, the stage of the tumor and the bone environment. This dual effect is also apparent at the level of the signal transducer and activator of transcription and the mitogen-activated protein kinases, the two main signaling pathways that mediate opposite effects in bone cells.