The aim of this paper was to discuss the arguments for and against the use of atypical antipsychotics in children and adolescents with aggression, and provide recommendations for future research. A MEDLINE search (1985-2004) was performed to identify key literature. Search terms included, but were not limited to, clozapine, olanzapine, quetiapine, risperidone, ziprasidone, children, and adolescents. The search was limited to English-language literature and randomized controlled trials. The use of atypical antipsychotics in children and adolescents has increased significantly over the past few years. Atypical antipsychotics are associated with a more favorable side-effect profile, and growing evidence supports their efficacy for aggression in this population. However, the long-term effects of these agents are unknown. No head-to-head evidence exists to suggest whether pharmacological or nonpharmacological treatments are superior for managing aggression associated with childhood and adolescent psychiatric and behavioral conditions. Future research of atypical antipsychotics in children and adolescents needs to evaluate not only the efficacy but also the effectiveness. Examination of treatment mediators and moderators may help to optimize treatment regimens and improve patient outcomes. Finally, effective interventions require the development and implementation of evidence-based treatment strategies using a multidisciplinary approach.