This review describes several limitations of the Digestible Indispensable Amino Acid Score (DIAAS) with a focus on its application to plant-based dietary patterns. Evaluating protein quality in terms of digestibility is paramount to support and optimize the health and well-being of human populations in situations where food insecurity and protein energy malnutrition are widespread. The Food and Agriculture Organization (FAO) of the United Nations has endorsed the DIAAS to replace the previously recommended Protein Digestibility Corrected Amino Acid Score (PDCAAS) for protein quality assessment. While multiple strengths characterize the DIAAS, substantial limitations remain, many of which are accentuated in the context of a plant-based dietary pattern. Some of these limitations include a failure to translate differences in nitrogen-to-protein conversion factors between plant- and animal-based foods, limited representation of commonly consumed plant-based foods within the scoring framework, inadequate recognition of the increased digestibility of commonly consumed heat-treated and processed plant-based foods, its formulation centered on fast-growing animal models rather than humans, and a focus on individual isolated foods vs the food matrix. The DIAAS is also increasingly being used out of context where its application could produce erroneous results such as exercise settings. When investigating protein quality, particularly in a plant-based dietary context, the DIAAS should ideally be avoided.