Attention-deficit/hyperactivity disorder (ADHD) assessment and treatment in children and adolescents is complex. Key biological and psychosocial risk factors need to be identified and treated because of their potential mediating interaction that affect the onset, progression, and psychosocial and medication treatment response of core ADHD symptoms and common associated co-morbid conditions. Both psychosocial and medication treatments, alone and in combination, have been shown to reduce the core ADHD symptoms and those of its key co-morbid disorders. Yet, to date, the potential synergism between targeted and specific medication and psychosocial treatments remains poorly understood and under-researched. Interestingly, recent positron emission tomography findings emphasise the importance of contextual salience and positive reinforcement strategies for stimulant medication, the primary medication treatment for ADHD, to have its effect. This is not surprising, given recent epigenetic models of gene–environment interaction that are revolutionising our understanding of developmental disorders like ADHD. This annotation briefly outlines the emerging evidence that supports the role of psychosocial treatment alongside medication treatment in the management of ADHD. Future significant clinical directions are noted.