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Better health depends on how well federal public health organizations perform both scientifically and organizationally. The performance challenges of public health science organizations are not carbon copies of those facing public service organizations. This article examines how one federal science agency in the public health field has instituted a performance orientation over a dozen years, offering a detailed illustration of how the in-principle advantages of the “managing for performance” approach can be realized in practice. In taking science more seriously as a basis for public policy, the new administration should not lose sight of lessons it can learn from its predecessors about managing science organizations for performance.