Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral disorder associated with a wide range of impairments. Psychostimulants are generally first-line pharmacotherapy, but symptom improvement is suboptimal in some patients. In these patients, clinicians frequently use a combination of psychostimulants and nonscheduled medications to manage ADHD, although published evidence supporting this practice was relatively scarce until recently.Guanfacine extended release (GXR), a selective alpha2A-adrenoceptor agonist, is approved as a monotherapy and adjunctive therapy to psychostimulant medications for ADHD in patients 6-17 years of age. Drug-drug interaction studies have demonstrated that the adjunctive administration of GXR with a long-acting methylphenidate preparation or lisdexamfetamine dimesylate did not change exposure to the active components of either medication in a clinically meaningful way compared with either treatment alone.Data supporting the potential efficacy of GXR adjunctive to psychostimulants were preliminarily observed in a 9-week, open-label, dose-escalation study and subsequent extension study (≤ 24 months) in subjects aged 6-17 years with suboptimal control of ADHD symptoms on psychostimulant monotherapy. In a subsequent 9-week, randomized, double-blind, placebocontrolled study of subjects aged 6-17 years with suboptimal response to a long-acting, extendedrelease, oral psychostimulant, adjunctive GXR (administered in the morning or evening) was associated with significantly greater symptom reduction than placebo and psychostimulant (ADHD Rating Scale IV [ADHD-RS-IV] total score, placebo-adjusted least squares mean reductions: GXR AM, -4.5, P = 0.002; GXR PM, -5.3, P < 0.001, based on Dunnett's test). Across multiple studies, the safety and tolerability profile of GXR administered adjunctively to psychostimulants has been consistent with the known profiles of each medication. Additional studies should further explore the role of adjunctive GXR in clinical practice to help identify those patients most likely to benefit from such therapy.