Clonidine, an α(2)-adrenergic agonist, is approved in the US as an extended-release (XR) tablet for the treatment of attention-deficit hyperactivity disorder (ADHD) in children and adolescents (aged 6-17 years). In two, randomized, double-blind, multicenter, phase III trials of 8 weeks' duration, clonidine XR improved the symptoms of ADHD in children and adolescents. Significantly greater reductions from baseline in ADHD rating scale IV (ADHD-RS-IV) total scores at week 5 (primary endpoint) were achieved by recipients of clonidine XR 0.2 and 0.4 mg/day monotherapy than by recipients of placebo. When added to patients' normal stimulant regimen, significantly greater reductions from baseline in ADHD-RS-IV total scores at week 5 (primary endpoint) were achieved with a flexible dose of clonidine XR 0.1-0.4 mg/day than with placebo. Symptomatic improvement of ADHD was achieved following 2 weeks' treatment with clonidine XR. In both trials, significantly greater reductions from baseline in ADHD-RS-IV total scores were apparent at week 2 onwards for recipients of clonidine XR than for recipients of placebo. Clonidine XR was generally well tolerated as monotherapy and as adjunctive therapy with stimulant regimens in clinical trials in children and adolescents.