Over 6 years, a U.S. Federal health agency, the Substance Abuse and Mental Health Services Administration, has developed a science-based communications strategy. Agency staff reviewed the scientific literature, discussed implications of it for meeting communications goals of the agency, created a strategy based on what was learned, and refined it over time as informed by experience. Doing so led to eight significant changes in ongoing operations of the agency’s Office of Communications. Discussion of these activities is followed by an analysis of possible next steps this agency or others like it could take to enhance communications strategy.