Attention-deficit hyperactivity disorder (ADHD) is defined as a clinically heterogeneous neurodevelopmental syndrome with the contribution of numerous genetic and environmental risk factors. The goal of interdisciplinary and translational neurobiological research is to clarify the interdependent relationship between molecular mechanisms and structural-functional substrates in the pathogenesis of ADHD and its significance to the disorder's long-term course. Work on ADHD-specific molecular genetic and developmental biological essentials of brain function and on the structural-functional basis of behavior holds the promise of developing predictors and differential strategies for effective therapy of severe and chronic courses of ADHD. To define evolutionary conserved ADHD-relevant principles of structure and function of the brain and behavior typical to the syndrome, an integrated approach in the elucidation of specific neuro- and psychobiological mechanisms and thus systemic pathophysiology of ADHD is crucial. Regarding compromised neurodevelopment, pathophysiological models of ADHD, particularly its syndromal and comorbid dimensions, therefore require the combination of molecular genetic, neuroimaging, neuropsychology, behavioral, and psychosocial strategies to explain complete causal chains.