To review the efficacy, safety, and abuse liability of approved treatments in adults with attention-deficit/hyperactivity disorder (ADHD), with a focus on once-daily medications. PubMed was searched for relevant studies/reviews in English from 2002 to 2011 on adult ADHD treatments. Keywords used in the search were ADHD, adults, and treatment. Limits included only clinical trials, meta-analyses, randomized controlled trials, and reviews including adults (aged ≥ 19 years). Selection criteria returned 471 publications. Retrieved studies were excluded if they primarily focused on children, treatments not indicated for ADHD, or ADHD and comorbid conditions. An epidemiologic survey revealed that 10.9% of adults identified with ADHD had received treatment during the prior 12 months. Treatments for ADHD in adults include pharmacologic and nonpharmacologic options. US Food and Drug Administration-approved long-acting stimulants and a nonstimulant with proven efficacy and safety profiles have been developed and include osmotic-release oral system methylphenidate hydrochloride (OROS-methylphenidate), extended-release dexmethylphenidate hydrochloride, mixed amphetamine salts extended release (MAS-XR), the nonstimulant atomoxetine hydrochloride, and the prodrug lisdexamfetamine dimesylate. Long-acting stimulants differ in formulation characteristics used to achieve extended release, with OROS-methylphenidate employing an osmotic-release technology, extended-release dexmethylphenidate hydrochloride and MAS-XR using pH-dependent beads, and lisdexamfetamine dimesylate using prodrug technology. These features variably affect pharmacokinetic characteristics, duration of action, and abuse liability. While all long-acting medications have varied pharmacokinetic features, mechanism of action, and duration of effect, all are generally efficacious and safety profiles are similar. Approved long-acting treatments in adults with ADHD were effective in improving symptoms and were generally well tolerated.