Objective: Internet-delivered cognitive behavior therapy programs have been developed and evaluated in randomized controlled trials during the past two decades to alleviate the rising demand for effective treatment of common mental health disorders such as anxiety and depression. While most of the research on internet-based cognitive behavior therapy (iCBT) has focused on efficacy and effectiveness only little attention has been devoted to the implementation of iCBT. The aim of this study was to identify the main implementation challenges perceived by therapists and managers involved in the practical operation of iCBT services in routine care settings in five European countries. Method: The study was designed as a multiple comparative case study to explore differences and similarities between five different iCBT services in Sweden, Norway, Denmark, The Netherlands and Scotland. Field visits were carried out to each of the five services including interviews with the management of the service (n = 9), focus group interviews with key staff (n = 15) and demonstration of online programs. The data material was processed through thematic, comparative analysis. Results: The analysis generated four transversal themes: 1) integration in the mental health care system; 2) recruitment of patients; 3) working practice of therapists; and 4) long-term sustainability of service. The main results concerned the need to address the informal integration in the health care systems related to the perceived skepticism towards iCBT from GPs and face-to-face therapists, the role of referral models and communication strategies for the stable recruitment of patients, the need for knowledge, standards and material for the training of therapists in the provision of online feedback, the need to improve the possibilities to tailor programs to individual patients, and the need for considerate long-term sustainability planning of the transitions from local projects to permanent regional or national services. Conclusion: The present study gives an overview of the main implementation challenges regarding the practical operation of iCBT services perceived by the therapists and managers of the iCBT services. Future studies into specific details of each challenge will be important to strengthen the evidence base of iCBT and to improve uptake and implementation of iCBT in routine care.