In this review, we will make a brief presentation of IL-18 and IL-18 binding protein (IL-18BP) biology, summarize the fundamental and translational work that has been conducted in the last two decades in this topic, and, finally, state how IL-18 and IL-18BP could be used in clinical practice, for the management of AOSD and sJIA. This evidence concerns the gene IL18 and adult-onset Still disease.