For over 20 years the National Heart, Lung, and Blood Institute (NHLBI) has supported community-based prevention research focused on cardiopulmonary risk-reduction. These prevention trials have involved intact groups in various major community settings as well as total communities. The mixed findings from these trials have advanced research and analytical methods, measurement approaches, and intervention strategies for community-based prevention studies and evidence-based public health practice. In addition, they have raised cross-cutting issues for the mukidisciplinary research teams working in this field. The purpose of this article is to summarize findings from a NHLBI conference including: 1) a description of where prevention trials in varying community settings fit in the NHLBI research continuum; 2) a summary of findings from prevention trials in major community settings including schools, worksites, health care practices, religious groups, and entire communities; 3) a summary of the issues for research design, analysis, and interventions: and 4) highlights of directions identified for practice, future research, and policy.