Interleukin (IL)-6 is a proinflammatory cytokine involved in various tumoral, autoimmune, inflammatory and infectious diseases. In particular, IL-6 is a major survival and proliferation factor of malignant plasma cells in patients with Multiple Myeloma (MM). IL-6 binds to a membrane receptor (IL-6R) or its soluble form (sIL-6R) and the complexes thus formed (IL-6/IL-6R or IL-6/s IL-6R) associate with a transducer gp130 molecule, resulting in the formation of high avidity IL-6 binding receptors, dimerization of gp130 and activation of transduction signals. This transducer chain is shared by 5 other cytokines of IL-6 family. In healthy individuals as well as in patients with IL-6 related diseases, high levels of agonist sIL-6R circulate, increasing the spectrum of IL-6 activities. In this survey, we discuss recent findings on the biology of soluble IL-6 and gp130 receptors, their involvement in various diseases, the possibility of neutralizing gp130 signaling by various antagonists of IL-6, IL-6R and gp130, or to activate gp130 signaling with agonist anti-gp130 monoclonal antibodies (mAb).