The authors conducted a systematic literature review of preventive pharmacological treatments for episodic childhood migraines searching several databases through May 20, 2012. Episodic migraine prevention was examined in 24 publications of randomized controlled trials that enrolled 1578 children in 16 nonrandomized studies. Single randomized controlled trials provided low-strength evidence that propranolol would result in complete cessation of migraine attacks in 713 per 1000 children treated (95% confidence interval, 452-974); trazodone and nimodipine decreased migraine days, while topiramate, divalproex, and clonidine were no more effective than placebo in preventing migraines. Migraine prevention with multidisciplinary drug management was not sustained at 6 months. Divalproex resulted in treatment discontinuation due to adverse effects, and topiramate increased the risk of paresthesia, upper respiratory tract infection, and weight loss. Long-term preventive benefits and improvement in disability and quality of life are unknown. No studies examined quality of life or provided evidence for individualized treatment decisions.