Despite the paucity of Food and Drug Administration-approved treatments, symptoms of irritability, hyperactivity, disruptive, and repetitive behaviors are common in youth with autism spectrum disorder (ASD). In North America and Europe, about half of youth with ASD receive pharmacologic treatment for psychiatric symptoms and co-occurring diagnoses. Moreover, the most commonly used medications in youth with ASD are antipsychotics, antidepressants, and ADHD medications. The selective serotonin reuptake inhibitor class of antidepressants is among the most commonly used psychotropic in this patient population, despite having limited evidence for their use, which we will explore further in this chapter. Polypharmacy is also common for children with ASD: per a study of Medicaid-eligible 8-year-olds, 41% with an ASD diagnosis were prescribed more than one psychotropic medication. For these reasons, and more, we find it important to summarize the evidence-based pharmacotherapies for youth with ASD and co-occurring psychiatric and behavioral disturbances.