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Autism spectrum disorder (ASD) has a high rate of psychiatric comorbidity. The prevalence of comorbid depression seems to correlate with higher functioning forms of ASD and increasing age. Adolescence is a time when youth struggle with identity and interpersonal relationships, and a diagnosis of ASD further complicates this process. Adolescents with ASD may be more aware of the social communication deficits that come with the diagnosis than children with ASD, and it is theorized that higher functioning adolescents may experience this more acutely. While this may be true, the lack of reliable rating and diagnostic scales for depression in individuals with ASD makes it difficult to accurately measure rates of depression among individuals with more severe verbal deficits. While some research has focused on the prevalence of comorbid depression in children and adolescents with ASD and on the associated risk factors, there is very little evidence guiding treatment, including no empirical studies on psychopharmacology for depression in this population. Available evidence exists only in psychosocial approaches to treatment at this time and is mostly limited to adult studies. Current evidence will be presented in this review, including prevalence rates of depression in youth with ASD, various risk and protective factors, the use of diagnostic rating scales, and treatment studies. The lack of evidence supporting various treatment approaches will be highlighted, including challenges specific to the treatment of depression in ASD, which are not addressed in the current treatment studies in typically developing youth with depression.