The majority of rigorous randomized double-blind placebo-controlled trials for pediatric BD have focused on acute mania. Relatively little is known regarding the pharmacological treatment of the depressive phase of BD,79 regarding the maintenance and/or continuation of treatment,80 or regarding other BD subtypes. Differences between adolescents and adults have been highlighted in a recent meta-analysis81 of acute mania trials, which included 5 trials (with 1140 participants) evaluating second-generation antipsychotics (SGAs; aripiprazole, olanzapine, quetiapine fumarate, risperidone, and ziprasidone hydrochloride) and 4 trials (with 469 participants) evaluating non-SGA mood stabilizers among youth. The SGAs appear to be more efficacious than the non-SGA mood stabilizers (divalproex sodium, lithium carbonate, and oxcarbazepine) among youth (effect size, 0.65 vs 0.20), whereas these agents are equally effective among adults (effect size, 0.48 vs 0.46). The SGAs are associated with greater weight gain, greater somnolence, and less akathisia among youth than among adults. Recent large-scale randomized controlled trials of oxcarbazepine and divalproex for pediatric mania have been negative,82 and a trial of topiramate was discontinued prematurely because of lack of efficacy for adult mania. Recent pharmacotherapy reviews since the AACAP treatment guidelines were published emphasize the role of SGAs as first-line treatments for mania, in part because of their rapid onset of action.83 Augmentation and combination treatment may involve various multimedication strategies, such as SGAs combined with lithium or divalproex.84 Nonadherence is common and appears to be associated with poorer outcomes.38 Significant concerns regarding the adverse metabolic consequences of these medications exist, and preliminary preventive strategies have been articulated.85,86 Metabolic monitoring guidelines for SGAs provide a strategy for early identification of adverse metabolic consequences, but, unfortunately, adherence with these guidelines is especially poor among youth. In addition to metabolic tolerability of mood-stabilizing medications, there are concerns about the potential for treatment-emergent mania or suicide-related behaviors among youth with BD who are treated with antidepressants or stimulants.87 For children with comorbid ADHD and BD, AACAP treatment guidelines recommend treating first with mood-stabilizing medication and only subsequently pharmacologically treating ADHD judiciously if there are residual clinically impairing symptoms of ADHD. Indeed, controlled studies suggest that this is an effective and well-tolerated approach.88 Similarly, it is advisable to first stabilize mood prior to initiating treatment with a selective serotonin reuptake inhibitor for the depressive phase of BD or for comorbid anxiety.84 Previous publications21,83,84 provide detailed approaches to selecting, evaluating, and monitoring psychotropic medications among youth with BD.