This paper identifies individual and systematic primary, secondary, and tertiary prevention approaches that can be used to enhance adherence in randomized controlled trials. Specifically, strategies such as these are discussed: careful screening during enrollment, use of a run-in period, fully informing participants of the study burden, explaining randomization, determining the participant's prior history with treatment interventions, establishing and using a tracking system, clearly specifying adherence measures, and staff training in communication and negotiation. These strategies have been gathered over time from our experiences working in multiple randomized controlled trials. Research on factors that promote or detract from adherence should be a standard part of randomized controlled trials. Control Clin Trials 2000;21:226S-232S