ADHD is one of the most important neurodevelopmental disorders in children and adolescents. The "gold standard" for treatment of this disorder is with methylphenidate (MPH). The response to this drug varies considerably. Up to 30% of the patients treated with this drug do not achieve the desired symptom relief, or they develop adverse reactions that require a shift to another drug. Most likely, genetic factors play an important role in determining the response to MPH. The identification of these genetic factors is required to personalise the drug treatment of ADHD. This will allow for improved treatment efficacy and reduce the risk of adverse reactions. So far, such factors have not been identified. This study proposal is aimed at discovering genetic factors affecting the response to MPH, as well as the identification of a genetic profile that can be used to predict the response to MPH. An unprecedented approach based upon systems biology that integrates bioinformatics and genomics will be used to achieve this goal. It is my aim that these results can be brought into the clinic to improve the treatment of ADHD and reduce the expenditures to the health care system.