Systemic juvenile idiopathic arthritis (sJIA) is a rare, systemic inflammatory disease classified as a subtype of JIA. Besides arthritis, it is characterised by systemic features such as spiking fever, skin rash, hepatosplenomegaly or serositis. It is becoming clear now that abnormalities in the innate immunity (cytokines such as interleukin (IL)-1, IL-6 and IL-18, and neutrophils and monocytes/macrophages rather than lymphocytes) play a major role in the pathogenesis of sJIA, distinguishing it from other JIA subtypes. Another distinctive feature of sJIA is its strong association with macrophage activation syndrome (MAS). Based on this, consensus is emerging that sJIA should be viewed as an autoinflammatory syndrome rather than a classic auto-immune disease. As a consequence of the progression in understanding the underlying mechanisms of sJIA, major changes in the management are evolving. So far, treatment has been based on glucocorticosteroids in combination with disease-modifying drugs such as methotrexate. Recently, remarkable improvement has been observed with IL-1 and IL-6 targeted therapies. These therapies might also change the long-term outcome of this disease. However, controlled trials set up in international collaboration are needed to determine the optimal treatment strategies for all sJIA patients.