Background: Attention Deficit Hyperactivity Disorder (ADHD) is highly prevalent in school age children worldwide and we need to improve response to atomoxetine drug (non stimulant ) which used for treatment of ADHD. Objective: This study was undertaken to Study of possibly existing genetic polymorphisms of (CYP2D6, CYP2C19) the main enzymes involved in atomoxetine metabolism and their relations with therapeutic response to atomoxetine in a sample of Egyptian children with ADHD disorder, and try to correlate their phenotype-genotype status. Patients and Methods: 150 children (100 cases+ 50 control) attended to outpatient pediatric neurology  clinic in  Bab Al Sha^' reya hospital of Al-Azhar University were evaluated by history, general and systemic examination stressing on neuro- psychatric examination, DSM-5 criteria for diagnosis of ADHD , Conner's Abbreviated Rating Scale for the follow up of ADHD and  genetic polymorphisms of CYP2D6 and CYP2C19 study by using  (PCR) / (RFLPS) techniques.  Results: There was genetic polymorphisms of the CYP2D6 and CYP2C19 enzymes in ADHD children  that  possibly influence the response  to atomoxetine, P <0.001. Conclusion: These results suggest that CYP2D6, CYP2C19 poor metabolizers taking atomoxetine optimal doses are likely to have greater efficacy, greater increases in side effects and some differences in tolerability compared with CYP2D6, CYP2C19 extensive metabolizers taking similar dose.