In the present review, we examine one of the critical issues that have been raised about evidence-based treatments and their portability to real-world clinical settings: namely, the presence of comorbidity in the participants who have been treated in these studies and whether the presence of comorbidity predicts or moderates treatment outcomes. In doing so, we examine treatment outcomes for the four most commonly occurring childhood psychiatric disorders: Anxiety disorders, affective disorders, attention deficit/hyperactivity disorder (ADHD), and oppositional defiant disorder (ODD)/conduct disorder (CD). For each of these disorders, we first review briefly the prevalence of comorbidity in epidemiological and clinical samples and then highlight the evidence-based treatments for these disorders. We next determine the effects of comorbidity on treatment outcomes for these disorders. For the most part, comorbidity in the treated samples is the rule, not the exception. However, the majority of studies have not explored whether comorbidity predicts or moderates treatment outcomes. For the not insignificant number of studies that have examined this issue, comorbidity has not been found to affect treatment outcomes. Notable exceptions are highlighted and recommendations for future research are presented.