Interleukin-6 (IL-6) is one of the most important proinflammatory cytokines that has a broad spectrum of immunoregulatory properties. The molecular mechanisms of signal transduction of IL-6 and its receptor, which have been previously established, were later supplemented with a concept of trans-signaling. The selective inhibition of this signaling cascade would allow the modulation of the pathological effects of IL-6. Reverse genetics methods helped to establish the physiological functions of IL-6 in normal state and in various diseases, including neoplasias. Therapeutic inhibitors of IL-6 or its receptor are already used to treat several autoimmune diseases; however, the systemic inhibition inevitably also neutralizes the protective functions of this cytokine. It is expected that, in the future, systemic therapy will be replaced by more specific and effective approaches that take into account the peculiarities of molecular signaling pathways in target cells and differences in the function of IL-6 depending on the cell source.