The symptoms of poor impulse control, impaired regulation of attention and locomotor hyperactivity in patients with attention-deficit hyperactivity disorder (ADHD) involve dysfunction of prefrontal cortical circuits. The prefrontal cortex (PFC) guides attention, actions, and emotions using representational knowledge, and is highly dependent on neurochemical state: moderate levels of dopamine (DA) D1 and norepinephrine (NE) alpha-2A (2A)-adrenoceptor stimulation are essential to strong prefrontal working memory function. ADHD is sometimes associated with genetic insults that dysregulate catecholamine signaling, for example reduced synthesis of NE is associated with poor sustained attention and impulse control. Approved treatments for ADHD (including stimulants, atomoxetine, and guanfacine) optimize catecholamine signaling in the PFC and strengthen PFC regulation of attention and impulse control. For example, low, therapeutic doses of methylphenidate increase levels of both NE and DA in the PFC in animals, enhance prefrontal physiology and cognitive function, and reduce locomotor hyperactivity in juvenile rats. These prefrontal actions likely contribute to methylphenidate’s therapeutic effects in ADHD. Deficits in PFC function underlie many of the symptoms of ADHD, including problems such as poor impulse control, weak sustained attention, heightened distractibility, and increased locomotor activity. The PFC in the right hemisphere is particularly important for inhibiting inappropriate responses [1], and both functional and structural imaging studies have shown weakness in this brain region in subjects with ADHD [2–5]. Basic research has shown that the PFC is especially sensitive to stimulation by the catecholamines NE and DA [6]. Importantly, all approved medications