Background: The safety profile of newer stimulant products is of interest. Because most studies focus on school-age children, there is also an increased interest in the treatment of other populations. Concern continues for the risk of substance abuse in the use of stimulants. Objective: The purpose of this paper is to review published data on the safety and tolerability of the newer forms of stimulants, treatment in special populations, and the risks of substance abuse and dependence in the treatment of attention deficit hyperactivity disorder. Methods: Literature obtained through Medline and Pubmed from 1995 were reviewed as well as key articles referenced in the literature. Conclusions: The use of the newer stimulant agents shows a safety profile of frequent, but usually mild side effects. They are generally safe in special populations. The risk of developing long-term substance abuse with attention deficit hyperactivity disorder, without co-morbidities, is small and may decrease with proper treatment. More research is needed.