Findings suggest that children and adolescents prescribed antipsychotics seem generally more susceptible to develop sedation, acute extrapyramidal side effects (EPSs), withdrawal dyskinesia, hyperprolactinemia, and age-inappropriate weight gain with related metabolic abnormalities. In children and adolescents, antipsychotics are being used in large and increasing quantities for a wide range of disorders and psychopathology, including psychotic, mood, and disruptive behavior disorders. Antipsychotics are also being used in children and adolescents to treat irritability associated with autism, tic disorders, obsessive-compulsive disorder, posttraumatic stress disorder and aggression; however the widespread use exceeds the database regarding efficacy as well as safety and tolerability in this population. Clinicians and researchers should use age-appropriate side effect measures that also take severity and time course of the adverse effects into account to help evaluate and manage more comprehensively antipsychotic risks and benefits in a given individual. Although antipsychotic safety and tolerability data in children and adolescents are limited and most extensive for risperidone, this is likely to change. Several large-scale, randomized placebo-controlled datasets have either been completed or are under way for all nonclozapine Second-generation antipsychotics (SGAs). In addition, a federally funded trial, the Treatment of Early Onset Psychosis Study, was recently completed that compared olanzapine, risperidone, and molindone. To counter randomization bias and provide safety and tolerability data in generalizable patient populations and settings, large-scale observational studies will also be helpful. Collectively, safety and efficacy data should inform a carefully weighed antipsychotic selection that takes general probabilities and patient/family preferences into account. Finally, because adverse effects are generally more easily predicted than therapeutic efficacy and because differences in efficacy between antipsychotics are generally smaller than those for adverse effects, initial treatment selection should be guided largely by varying adverse effect profiles across agents. Tables, references