The variable expression of autism over the lifespan is likely to lead to different symptoms and support requirements, and to distinct responses to pharmacotherapy treatment, in older patients compared to children. This systematic review considers the effectiveness of pharmacological treatment in managing autism spectrum disorder in adolescents and adults. Following a comprehensive search of literature published in English from 1980, methodological criteria were applied to identify studies designed to reliably assess treatment effectiveness. Only five double-blind, randomized controlled trials were eligible for appraisal. All had small sample sizes (mean = 30) and brief treatment duration of no more than 12 weeks. The paucity of trials and their methodological limitations means that there is only preliminary evidence about the short-term effectiveness of a few drug treatments for this age group. There was also a lack of reliable data reported on drug safety profiles. Methodological challenges and directions for future research are discussed. (Contains 1 table and 1 note.)