We reviewed the literature of medication trials in ADHD to evaluate the scope of the available non-stimulant treatments. A variety of compounds with a common noradrenergic/ dopaminergic activity have shown documented anti-ADHD activity. There is a substantial body of literature documenting the efficacy of tricyclic antidepressants on ADHD in over 1,000 subjects. In addition, the atypical antidepressant bupropion and the novel noradrenergic specific antidepressant tomoxetine have also been documented to be effective in the treatment of ADHD in controlled clinical trials. Despite wide use, the scientific base supporting the efficacy of alpha-2, noradrenergic agonists continues to be limited. Several lines of evidence provide preliminary support for the potential benefits of cholinergic cognitive enhancing drugs in such as anticholinesterase inhibitors (tacrine, donepezil) as well as novel nicotinic analogues (ABT-418). Despite these promising results, more research is needed on alternative pharmacologic treatments for the treatment of ADHD.