Purpose of review Biological drugs that target the inflammatory cytokine interleukin-6 (IL-6) are increasingly considered as therapies for chronic disease and cancer. The purpose of this review is to place the biology of IL-6 in context. Here, we provide information on the biology behind IL-6 and consider mechanisms that are relevant to the application of IL-6 targeted therapies. Recent findings The clinical blockade of IL-6 activity with tocilizumab has fuelled considerable interest in the biology behind this inflammatory cytokine. Although IL-6 impacts both innate and adaptive immunity, and the control of tissue homeostasis, the signalling mechanisms that control IL-6 responsiveness are complex. Several alternative IL-6-directed interventions with unique modes of action are now approaching the clinic. However, various questions still remain about how and when to block IL-6. Owing to the complexity of IL-6 biology, this is not trivial. In this review, we introduce the immunobiology of IL-6 and explore the different therapeutic strategies in development that inhibit IL-6 activity. Summary Various inhibitors of IL-6 bioactivity are now in development of routine clinical practice. The key is to understand how best to apply these drugs. This review provides useful insight into the workings of IL-6 in health and disease.