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Plants offer a vast source of bioactive chemicals with the potential to improve human health through the prevention and treatment of disease. However, many potential therapeutics are produced in small amounts or in species that are difficult to cultivate. The rapidly evolving field of plant synthetic biology provides tools to capitalize on the inventive chemistry of plants by transferring metabolic pathways for therapeutics into far more tenable plants, increasing our ability to produce complex pharmaceuticals in well-studied plant systems. Plant synthetic biology also provides methods to enhance the ability to fortify crops with nutrients and nutraceuticals. In this review, we discuss (1) the potential of plant synthetic biology to improve human health by generating plants that produce pharmaceuticals, nutrients, and nutraceuticals and (2) the technological challenges hindering our ability to generate plants producing health-promoting small molecules., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Barnum, Endelman and Shih.)