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Neurologic and psychiatric manifestations are prevalent in children and adults with lupus (labeled by convention neuropsychiatric systemic lupus erythematosus or NPSLE). However, there is a paucity of data on the evaluation and management of NPSLE in youth, with only a few publications describing the use of atypical antipsychotics in children and adolescents with lupus. In children, aripiprazole, a D2/5-HT1A partial agonist, appears to cause less prominent metabolic derangements than other second-generation antipsychotics. This agent may be an important tool in the treatment of pediatric patients with lupus who are at risk for weight gain and dyslipidemia due to disease and corticosteroid effects. The authors present two cases in which psychiatric symptoms associated with treatment-refractory lupus responded to aripiprazole pharmacotherapy.