Brady and Kendall (1992) concluded that although anxiety and depression in youths are meaningfully linked, there are important distinctions, and additional research is needed. Since then, studies of anxiety-depression comorbidity in youths have increased exponentially. Following a discussion of comorbidity, we review existing conceptual models and propose a multiple pathways model to anxiety-depression comorbidity. Pathway 1 describes youths with a diathesis for anxiety, with subsequent comorbid depression resulting from anxiety-related impairment. Pathway 2 refers to youths with a shared diathesis for anxiety and depression, who may experience both disorders simultaneously. Pathway 3 describes youths with a diathesis for depression, with subsequent comorbid anxiety resulting from depression-related impairment. Additionally, shared and stratified risk factors contribute to the development of the comorbid disorder, either by interacting with disorder-related impairment or by predicting the simultaneous development of the disorders. Our review addresses descriptive and developmental factors, gender differences, suicidality, assessments, and treatment-outcome research as they relate to comorbid anxiety and depression and to our proposed pathways. Research since 1992 indicates that comorbidity varies depending on the specific anxiety disorder, with Pathway 1 describing youths with either social phobia or separation anxiety disorder and subsequent depression, Pathway 2 applying to youths with coprimary generalized anxiety disorder and depression, and Pathway 3 including depressed youths with subsequent social phobia. The need to test the proposed multiple pathways model and to examine (a) developmental change and (b) specific anxiety disorders is highlighted.