Put into context, bipolar disorder is a devastating illness that affects up to 5% of the adult population (3). It often has its onset in childhood and adolescence (4). Furthermore, early-onset bipolar disorder may be a particularly severe form of the illness (4, 5). Identifying and treating bipolar disorder as early as possible in youth therefore has huge potential to improve the course of illness. Yet, sometimes this can be extremely difficult using current clinical methods, for two main reasons. First, there is considerable overlap between symptoms of bipolar disorder and symptoms of other psychiatric illnesses (6). Many bipolar disorder symptoms, such as irritability, motor hyperactivity, and sleep problems, overlap with other, more common pediatric psychiatric illnesses, including ADHD. As early-onset bipolar disorder is associated with worse symptom and functional outcomes in adulthood, intervening with effective treatment before the illness can permanently damage long-term outcome is an important public health goal. Misdiagnosing bipolar disorder as ADHD could therefore result in exposure to psychostimulant medications in bipolar youth, without the protective effect of mood stabilizing medications. On the other hand, overdiagnosis of bipolar disorder could lead to inappropriate treatment with mood stabilizers and antipsychotic medications in youth who may have ADHD. Other psychiatric illnesses that might be difficult to differentiate from bipolar disorder, such as conduct disorder, major depressive disorder, or anxiety disorders, may even be effectively treated by psychosocial interventions instead of medications. A second reason for the difficulty in accurately diagnosing bipolar disorder in youth is that many children and adolescents present in community, clinical, and research settings with what appear to be significant manic symptoms but do not meet DSM-IV criteria for bipolar disorder. For these youth, differentiating between bipolar disorder and other illnesses, such as severe mood dysregulation, is extremely difficult.