OBJECTIVE: The Internet is a frequently used platform for research in pediatric and health psychology. However, there is little pragmatic guidance as to ethical best practice of this research. The absence of guidance is particularly prominent for online research with children. Our objective is to outline ethical issues in e-health research with children and adolescents using two exemplar studies in pediatric pain research. METHODS: The first study is an asynchronous message board discussion amongst teenagers with pain who are frequent internet users.The second study is a web-based behavioral intervention for the management of adolescent pain. RESULTS: Each exemplar study is discussed in the context of specific ethical considerations related to recruitment, informed consent and debriefing, privacy and confidentiality, and participant safety. Ethical issues regarding the evaluation of online psychological interventions are also discussed. CONCLUSIONS: Guidance on optimal ethical practice in e-health research is summarized.