Five to 40% of children and adolescents with attention deficit hyperactive disorder (ADHD) also have comorbid major depressive disorders (MDD). Moreover, youths with ADHD have up to a 4 times higher risk of developing depressive disorders than the general adolescent population. Comorbidity with MDD has been associated with elevated impairment and higher rates of hospitalization versus ADHD alone. However, depression in youths with ADHD may be more difficult to diagnose, given that some symptoms overlap between the two disorders. Moreover, many of the medications used to treat ADHD cause side effects resembling symptoms of MDD. Available studies suggest the particular importance of anhedonia, social withdrawal, psychomotor retardation, negative views of self and future, and suicidal thoughts as symptoms that distinguish MDD in youths who have ADHD. Despite ongoing controversy, the view that pediatric bipolar disorder (PBD) is rare or non-existent has been increasingly challenged not only by case reports but also by systematic research; however, a significant portion of bipolar youth, especially children, have high comorbidity with ADHD. Significant debate exists on whether early onset bipolar disorder is mistakenly attributed to attention deficit hyperactivity disorder (ADHD), or whether ADHD is frequently misdiagnosed as mania. Among pediatric-onset cases of bipolar disorder, comorbid ADHD is frequently seen, and there is strong evidence to suggest that this pattern has a familial and genetic basis. Differentiating bipolarity in children with ADHD is not an academic discussion but also a great concern because of the associated complication of the treatment of these disorders. It is suggested that manic symptoms should represent a distinct change from a child's usual level of functioning (e.g., change or worsening of distractibility during a mood episode in children with ADHD). There are some symptoms that mainly occur in BD youth as compared to other disorders (e.g., ADHD) and may help to differentiate between BD and these disorders, such as clinically relevant euphoria, grandiosity, decreased need for sleep, hypersexuality (without history of sexual abuse or exposure to sex), and hallucinations. We need larger longitudinal studies to better understand the risks and resilience factors of developing BP in ADHD youth.