There have been a number of major advances in the treatment of systemic lupus erythematosus and we are now in the era of biologic therapies for this multisystem autoimmune disorder. There has been a greater awareness of the toxicities of the traditional therapies including the recognition that the doses of corticosteroids used in the past have been excessive, resulting in unacceptable toxicities. Other advances have included the development of lower cumulative doses of cyclophosphamide and the widespread acceptance of mycophenolate mofetil for the treatment of lupus nephritis. This review addresses the current management of severe lupus with corticosteroids and cytotoxic agents.