Background: Open access websites which deliver cognitive and behavioral interventions for anxiety and depression are characterised by poor adherence. We need to understand more about adherence in order to maximize the impact of Internet-based interventions on the disease burden associated with common mental disorders. Objective: The aims of this paper are to review briefly the adherence literature with respect to Internet interventions and to investigate the rates of dropout and compliance in randomized controlled trials of anxiety and depression Web studies. Methods: A systematic review of randomized controlled trials using Internet interventions for anxiety and depression was conducted, and data was collected on dropout and adherence, predictors of adherence, and reasons for dropout. Results: Relative to reported rates of dropout from open access sites, the present study found that the rates of attrition in randomized controlled trials were lower, ranging from approximately 1 - 50%. Predictors of adherence included disease severity, treatment length, and chronicity. Very few studies formally examined reasons for dropout, and most studies failed to use appropriate statistical techniques to analyze missing data. Conclusions: Dropout rates from randomized controlled trials of Web interventions are low relative to dropout from open access websites. The development of theoretical models of adherence is as important in the area of Internet intervention research as it is in the behavioral health literature. Disease-based factors in anxiety and depression need further investigation. [J Med Internet Res 2009;11(2):e13]