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The objective of this study was to review the evidence about what factors influence user engagement in Internet-based behavioral interventions for chronic illness. We conducted a systematic review of the recent published literature. Searches of MEDLINE (using Ovid and PubMed), The Cochrane Library, and PsycINFO, from January 2000 to December 2008, were completed. Additional articles were identified from searching the bibliographies of retrieved articles. We identified studies of interactive health communication interventions delivered via the Internet that, apart from delivering health information, had another component such as interactive tools to manage illness, decision support for treatment, or social support. We restricted the age range to adulthood. The search identified 186 abstracts; 46 articles were reviewed. We used a qualitative approach called "positive deviance" to study those interventions that have succeeded in engaging users where most have failed. Some ways to improve user engagement in Internet interventions suggested by our review include addressing health concerns that are important and relevant to an individual patient or consumer and an individualized approach, such as personally tailored advice and feedback. Interventions that are part of larger health management programs that include clinicians appear to be especially promising.