An increasing number of antipsychotic medications have demonstrated efficacy in randomized placebo-controlled trials in the treatment of children and adolescents with schizophrenia. This review summarizes and synthesizes relevant antipsychotic medication studies, with particular emphasis on second-generation agents, and discusses other clinical considerations that may influence medication selection. With the exception of clozapine demonstrating superior efficacy in the improvement of psychotic symptoms in treatment-resistant patients, many antipsychotic agents have been shown to be similarly efficacious, including first-generation medications. Consideration of the side-effect profile, which can differ substantially from medication to medication, is essential when choosing treatment options.