For the fourth time in twelve months, the U.S. Department of Health and Human Services (HHS) has released a new version of its Grants Policy Statement (GPS) effective October 1, 2025. Prior to these changes, the GPS had remained unchanged since 2007. These recent revisions to the GPS, including the latest one, integrated the GPS and the Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards (Uniform Guidance), an action that was long overdue. Thus, while many of the changes are new to the HHS GPS, they are not new to grant recipients. Rather, the GPS updates reflect the Uniform Guidance requirements that have long applied to HHS awards. This article addresses key changes to the GPS pursuant to its alignment with the Uniform Guidance while also noting a few minor revisions that reflect the new administration’s priorities.