The aim of this paper is to evaluate the use of non-stimulants, including atomoxetine, bupropion and modafinil, as alternative approaches to the treatment of children with attention-deficit hyperactivity disorder. A comprehensive review of the empirically based literature regarding the efficacy and the safety of the non-stimulants was performed. There is a large and increasing body of data supporting the efficacy and the safety of non-stimulants. Although the treatment effect sizes for non-stimulants may be smaller than those for stimulants, non-stimulants alone have been shown to be effective in the treatment of attention-deficit hyperactivity disorder as well as several comorbidities. These results suggest that non-stimulants are effective in the treatment of attention-deficit hyperactivity disorder. Further studies are needed to improve our understanding of alternative pharmacological medications in the treatment of attention-deficit hyperactivity disorder.