A Medicaid statewide quality improvement (QI) collaborative was developed to improve antipsychotic prescribing practices for children. With use of a multistrategy approach that incorporated data-driven feedback and evidence-based recommendations, improvements were seen in three measures: antipsychotics prescribed to children under age six, prescription of two or more concomitant antipsychotics for longer than two months, and prescription of four or more psychotropic medications. Challenges and complexities are reviewed, including use of ongoing QI to address factors influencing antipsychotic prescribing behaviors, engagement of providers in QI efforts, and financial sustainability of such efforts.