This paper reviews key challenges in evaluating eHealth intervention and behavior change programs, and makes recommendations for the types of designs, measures, and methods needed to accelerate the integration of proven eHealth programs into practice. Key issues discussed include evaluation approaches that answer questions that consumers, potential adoptees, and policymakers have. These include measures of participation and representativeness at both patient and healthcare setting levels, consistency of outcomes across different subgroups, tendency of an eHealth program to ameliorate versus exacerbate health disparities, implementation and program adaptation, cost, and quality-of-life outcomes. More practical eHealth trials are needed that use rigorous but creative designs compatible with eHealth interventions and theory. These evaluations should address key dissemination issues, such as appeal, use, and robustness of eHealth programs across different subgroups, settings, conditions, outcomes, and time.