BACKGROUND: Modafinil is an alerting agent approved for the treatment of narcolepsy in adults. There are no studies examining the long-term effects and safety profile of modafinil in children with excessive daytime somnolence (EDS). OBJECTIVES: To determine the effects of modafinil on clinical manifestations of narcolepsy and idiopathic hypersomnia. METHODS: A systematic chart review was conducted for 13 children (mean age 11.0+/-5.3 years, six males, 10 with narcolepsy and three with idiopathic hypersomnia) receiving modafinil. RESULTS: The mean modafinil dose was 346+/-119 mg/day, with a mean treatment duration of 15.6+/-7.8 months. For approximately 90% of the children treated, parents reported a favorable response with the reduction in sudden sleep attacks, as documented by sleep-wake diaries. One child failed to improve on 400 mg/day modafinil and was switched to methylphenidate. Two other children showed only partial improvement and required additional stimulant medication to control EDS symptoms. Seven children underwent repeated nocturnal polysomnography and multiple sleep latency tests (MSLT). Compared to baseline MSLT measures (mean sleep latency: 6.6+/-3.7 min), modafinil prolonged mean sleep latency (10.2+/-4.8 min, p=0.02) without significant alteration in nocturnal polysomnographic measures. However, a trend towards REM sleep reduction was noted (16.8+/-5.1%TST vs. 11.8+/-6.2%TST). Exacerbation of seizures and psychotic symptoms was reported with modafinil therapy in two children with preexisting conditions. Hematological and hepatic functions assessed every 3 months remained unaltered. CONCLUSION: Modafinil has a modest, yet significant effect on EDS in children and appears to be safe and well tolerated.