The effectiveness of e-health interventions varies greatly. Despite this, there has been relatively little formal consideration of how differences in the design of an intervention (i.e., how the content is delivered) may explain why some interventions are more effective than others. This review primarily examines the use of the Internet to provide educational and self-management interventions to promote health. The article develops hypotheses about how the design of these interventions may be associated with outcomes. In total, 52 published reports from both a diversity sample and a representative sample were reviewed using techniques from Critical Interpretive Synthesis. Four core interactive design features were identified that may mediate the effects of intervention design on outcomes: Social context and support, contacts with intervention, tailoring, and self-management. A conceptual framework to summarize the design of e-health interventions delivered using the Internet is proposed. The framework provides a guide for systematic research to identify the effects of specific design features on intervention outcomes and to identify the mechanisms underlying any effects. To optimize the design of e-health interventions more work is needed to understand how and why these design features may affect intervention outcomes and to investigate the optimal implementation and dosage of each design feature.