Childhood psychotic symptoms are worrisome and difficult to assess. Childhood Onset Schizophrenia (COS) is a rare illness that requires differentiation from other conditions that present with psychotic features. Although there are neuro-anatomic distinctions, providers need clinical criteria to more accurately diagnose and plan treatment and family work is a key factor in stabilization. The primary objective of this Clinical Case Conference is to review clinical criteria for assessing psychotic symptoms in children with a goal of delineating the most critical for diagnosing schizophrenia. The program also offers a framework for evaluating children with these symptoms. The current data and imaging from the National Institute of Mental Health COS research group is presented to illustrate the neurobiological features of COS, compared to normal controls and those children with non-schizophrenia psychotic illnesses.