The prevalence of Attention-deficit/hyperactivity disorder (ADHD) is about 6% in adults and 10% in children and adolescents in the United States. Approximately 66% of children and 75% of adults have comorbid psychiatric conditions. Major Depressive Disorder and Bipolar Disorder are two common comorbidities. Symptoms of ADHD and comorbid mood disorders may overlap, making it difficult to diagnose comorbid conditions. Furthermore, patients with mood disorders who do not respond to antidepressant treatment may have undetected ADHD. Those patients are more likely to have a poor response to initial depression treatment. Differences in symptoms of emotional dysregulation and mood disorders will be defined. Best practices for evaluation and pharmacological treatment of ADHD and comorbid mood disorders will be presented. Data from combined pharmacotherapy trials for ADHD and comorbid mood disorders will be presented. Combination medications for ADHD can be safely prescribed to patients with mood disorders. The order in which the disorders are treated does vary by diagnosis and symptom severity. Case examples will guide the learner through evaluation and treatment of ADHD and comorbid mood disorders.