A variety of medical conditions can present, or be associated, with psychiatric symptoms. At times, these may be so prominent that they can overshadow the underlying pathophysiologic process that accounts for them. Thus, it is equally important for mental health providers to be alert to the possibility that adolescents whom they are treating may have symptoms related to a treatable medical condition as it is for primary care providers to conduct a targeted history and physical examination with their adolescent patients exhibiting psychiatric symptoms. Using the biopsychosocial approach, these two domains are not considered separately or hierarchically, but as highly interactive. In some cases (eg, adrenal insufficiency), appropriate and continued treatment of the underlying condition results in resolution of the psychiatric symptoms. In others (eg, SLE), treatment of the underlying condition may alleviate but may also exacerbate psychiatric symptoms. Therefore, comprehensive treatment of adolescents with psychiatric symptoms due to a medical condition may require the professional services of primary care, mental health, and specialty care providers, but their services should follow the collaborative model espoused throughout the other articles in this volume.