The Internet is a rich multimodal communication environment where researchers can often recruit large numbers of participants for survey studies at low cost; however, there are many unanswered questions about the use of this technology in medical research. An important question is whether the results obtained in such surveys are generalizable to other populations. In this article, we describe different approaches for recruitment of participants on the Internet and how specific approaches may limit generalizability. Another issue clouding use of the Web in research is the essential anonymity of participants. We discuss the risk and benefits of anonymous surveys and technical methods that minimize the risks while preserving anonymity and confidentiality. A related problem may be accidental or deliberate enrollment of unqualified individuals in studies. Researchers can use survey design and statistical methods described herein to partially address threats to validity arising from such individuals; however, in some situations, confirmation of eligibility, by manual review of medical records, may be necessary.