Owing to environmental, ethical, health, and safety concerns, there has been considerable interest in replacing traditional animal-sourced foods like meat, seafood, egg, and dairy products with next-generation plant-based analogs that accurately mimic their properties. Numerous plant-based foods have already been successfully introduced to the market, but there are still several challenges that must be overcome before they are adopted by more consumers. In this article, we review the current status of the science behind the development of next-generation plant-based foods and highlight areas where further research is needed to improve their quality, increase their diversity, and reduce their cost, including improving ingredient performance, developing innovative processing methods, establishing structure-function relationships, and improving nutritional profiles. Expected final online publication date for the Annual Review of Food Science and Technology, Volume 15 is April 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.