Systemic juvenile idiopathic arthritis (JIA) is an autoinflammatory condition that is distinct from other forms of childhood arthritis. Recently, biologic agents that specifically inhibit the cytokines interleukin (IL)-1 and IL-6 have demonstrated remarkable clinical effectiveness and confirmed the importance of these cytokines in the disease process. Future studies are likely to optimize the care of children with systemic arthritis and further elucidate the disease pathogenesis.