On October 18, 2021, the US Department of the Treasury released The Treasury 2021 Sanctions Review, a report that, based on an analysis of US sanctions imposed over the last 20 years, offers recommendations on how to preserve and enhance the effectiveness of sanctions. The report is the product of Secretary of Treasury Janet Yellen’s commitment during her confirmation hearing to engage in a comprehensive review of US sanctions. The review confirmed that sanctions continue to be an effective policy tool to address threats to the national security, foreign policy and the economy of the US. However, the Treasury Department has faced new challenges in recent years stemming from a prevalence of cybercrime, risks posed by alternative payment platforms, and the growing use of digital currencies and assets that collectively have had unintended impacts on US and allied workers and businesses and the flow of legitimate humanitarian aid to those in need around the world, highlighting a need for modernization. Towards this end, the review proposes a few key recommendations to modernize the current program. These include the adoption of a structured policy framework with clear policy objectives; the adoption of multilateral coordination whenever possible; the imposition of sanctions that are easily understood, enforceable, and reversible; and the calibration of sanctions in order to mitigate unintended economic and political impacts to humanitarian operations and non-targeted populations.