In adolescents, antipsychotics are most often used to treat complex, comorbid conditions with core disruptive features. However, the literature guiding such practices is limited. Best practice guidelines bridging the gap between the evidence and clinical practice have been developed to promote the appropriate and safe use of antipsychotics in aggressive youths. Due to complex barriers that exist at the level of the physician, patient/family and organization, merely disseminating these guidelines will not likely change antipsychotic prescribing practices. Negative attitudes, time constraints, lack of staff training and resources, or adolescent/family nonadherence can impede the translation of best practice guidelines into routine practices. Efforts to implement best practice guidelines must address these barriers if changes in prescribing practices are to occur and be sustained.