Systemic Lupus Erythematosus (SLE) of childhood is a complex and challenging disease which can occur at any age. Identification of disease early in it's course and aggressive, appropriate management leads to improved outcome for an individual child. The history of SLE indicates how much progress has been made in the last quarter century. A discussion of the etiopathogenesis of SLE demonstrates the complexity of the syndrome. This is followed by a description of clinical manifestations, including diagnostic criteria, differential diagnosis and suggested methods for eliciting important symptoms to make the diagnosis. Evaluation of specific organs is next reviewed highlighting critical organ manifestations that are significant for future prognosis. Treatment of SLE includes a variety of medications, including non-steroidal anti-inflammatory medications, steroids and immuno-suppressive drugs. Attention to physical activity, stress and nutrition is equally important. Signs and symptoms that indicate disease flare or infection are described. Lastly, related syndromes are reviewed.