Recent evidence suggests that individuals with autism spectrum disorder (ASD) experience depression at rates approximately four times greater than the general population. Co-occurring mood problems, including depressive and bipolar disorders, are associated with negative outcomes such as lower quality of life, increased adaptive behavior impairments, and greater service use. This chapter discusses what is known about the presentation of unipolar and bipolar depression in people with ASD and describes challenges to establishing sound prevalence estimates of mood disorders in ASD as they relate to methodological design issues and diagnostic assessment practices. It also provides an overview of potential vulnerability factors in the development of depression in this population; these areas of vulnerability include characteristics such as chronological age, cognitive ability, and ASD symptom severity, as well as those individual differences that may represent more direct mechanisms, for example, maladaptive coping styles, attentional biases, social reward profiles, and predisposition to rumination. The current research on interventions specifically designed to treat mood in people with ASD is very limited. However, promising treatments include adapted cognitive behavioral therapy and mindfulness-based approaches. Though most of this chapter focuses on unipolar depression in ASD as the more well-studied mood disorder, the chapter also summarizes the small research base on bipolar disorder in the context of ASD. It ends with a call for improved screening, assessment, and evidence-based treatment options to address this significant public health problem in this special population.