Attention-deficit/hyperactivity disorder (ADHD) is a common mental disorder caused by abnormal regulation of noradrenergic and dopaminergic neurotransmission. In some patients, symptoms persist throughout life, making each area of daily living challenging and impairing overall functioning. In addition to psychotherapy, treatment includes pharmacotherapy in the form of psychostimulants (amphetamine and methylphenidate) and non-stimulants (atomoxetine). The function of the drugs is to improve neurotransmission and reduce symptoms. The purpose of this article is to compare the efficacy, tolerability and safety of methylphenidate and atomoxetine for adult ADHD patients. A systematic literature search was performed using databases such as PubMed, PsycINFO, and Google Scholar. 31 clinical trials were included, 10 concerned the effect of methylphenidate, 8 the atomoxetine and the remaining studies effectiveness of both of them. A comparative analysis of the effects of methylphenidate and atomoxetine indicates their effectiveness in reducing symptoms among adults with ADHD. Atomoxetine was shown to be superior in reducing hyperkinetic symptoms and in patients with severe symptoms. Both drugs are well tolerated and safe to use.