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This article provides an overview of the U.S. bioeconomy, discussing how its definition has evolved and been formalized over time. The first attempts to conceptualize and define the U.S. bioeconomy began in the early 1990s. This was followed by a series of government and private efforts to develop methods to understand and evaluate it and to develop programs to promote it. These efforts culminated in the 2020 release of the National Academies of Science, Engineering, and Medicine (NASEM), Safeguarding the Bioeconomy report. The report recommended a formal definition of the U.S. bioeconomy, providing the rationale for that particular definition in the U.S. context. Formally adopting a comprehensive definition of the U.S. bioeconomy would enable the U.S. government to better assess the bioeconomy’s current state, to develop strategies to support its growth, and to promote strategies to safeguard it. Along with this recommendation, the NASEM Safeguarding report also discussed defining the “bioeconomy landscape,” which involves more precise determination and quantification of which economic activities are part of and external to the U.S. economy. Defining this landscape could guide metric development and data collection needed to track the bioeconomy’s growth, conduct economic assessments, and enable policy makers to keep abreast of advances that could potentially pose new national or economic security challenges. The report also includes an analysis of the broad range national bioeconomy strategies, identification of the four drivers of the U.S. bioeconomy, and the first of its kind, comprehensive estimate of the size and scope of the U.S. bioeconomy of USD 959B (valued in 2016 constant USD ).