Proinflammatory cytokines are centrally involved in the pathogenesis of various rheumatic diseases. Interleukin (IL)-6 is a prototypic representative of this family. Basic research has uncovered a multitude of functions for this cytokine, such as immune regulation, hematopoiesis, inflammation, and oncogenesis (Fig. 1). In recent years, agents blocking the actions of IL-6 have been developed for the therapy of rheumatologic inflammatory diseases. While in some diseases, most notably rheumatoid arthritis, the clinical efficacy of these drugs was excellent, the results of clinical trials in other chronic inflammatory diseases were heterogeneous. In this review, we will summarize the data currently available on IL-6 blockade in chronic inflammatory diseases and will also discuss the safety issues of blocking this cytokine.