Systemic juvenile idiopathic arthritis (sJIA) constitutes a small part of juvenile idiopathic arthritis (JIA), yet has a disproportionally higher rate of mortality. Despite being grouped under JIA, it is considered to be a multifactorial autoinflammatory disease. The objective of this paper is to review the epidemiology, pathogenesis, genetics, clinical manifestations, complications, therapy, prognosis, and outcome of sJIA. The presentation and clinical manifestations of sJIA have not changed much in the past several decades, but the collective understanding of the pathogenesis and the development of new targeted therapies (particularly the biologic agents) have transformed and improved the disease outcome for children with sJIA.