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Internet-delivered cognitive behavioral therapy (iCBT) was developed to overcome some of the barriers in accessing best practice face-to-face CBT. iCBT affords many benefits, such as high fidelity, greater accessibility, convenience, and reduced cost to patients and health-care systems. Recent meta-analyses of iCBT for depressive and anxiety disorders demonstrate large effect size for superiority of iCBT over control conditions (ES>.95; number needed to treat (NNT) = 2) and data collected in routine practice supports the effectiveness of these programs. Tailoring treatment to match patient variables may be one means to increase adherence and optimize clinical outcomes. However, we propose that a “personalized medicine” approach will require looking beyond patient characteristics and comorbidities to consideration of the cognitive processes that subserve depression and anxiety symptomatology.