This systematic review examines treatment guidelines, efficacy/effectiveness, and tolerability regarding the use of antipsychotics concurrently with psychostimulants in treating aggression and hyperactivity in children and adolescents. Articles examining the concurrent use of antipsychotics and psychostimulants to treat comorbid attention deficit/hyperactivity disorder (ADHD) and disruptive behavior disorders (DBDs) were identified and their results were summarized and critically analyzed. Antipsychotic and stimulant combination therapy is recommended by some guidelines, but only as a third-line treatment following stimulant monotherapy and stimulants combined with behavioral interventions to treat aggression in patients with ADHD. Some studies suggest efficacy/effectiveness for an antipsychotic and stimulant combination in the treatment of aggression and hyperactivity in children and adolescents. However, the data do not clearly demonstrate superiority compared to antipsychotic or psychostimulant monotherapy. Most studies were performed over short time periods, several lacked blinding, few studies used any placebo control, and no comparisons were made with behavioral interventions. There are concerns about the tolerability of combination therapy, but data do not suggest significantly worse adverse effects for combination compared to either antipsychotic or stimulant monotherapy. Conversely, and contrary to speculation, use of a stimulant does not significantly reduce metabolic effects of antipsychotics. Combination treatment with antipsychotics and psychostimulants is used frequently, and increasingly more often. Few studies have directly examined this combination for the treatment of ADHD and DBDs. Further studies are necessary to confirm the efficacy and tolerability of the concurrent use of antipsychotics and psychostimulants in children and adolescents.