The use and impact of low-calorie sweeteners (LCS) in relation to the national challenges of overweight and obesity are complex and controversial. Most research on LCS have focused on the prevalence of consumption of LCS in beverages. The 2015 Dietary Guidelines Advisory Committee emphasized dietary patterns and health rather than a focus on specific nutrients or foods. The committee took this approach to shift the national emphasis onto the context of total rather than individual nutrient consumption. A broader research paradigm is needed to elucidate the actual exposure to LCS and how they are consumed within dietary patterns in the US population. National-level databases exist that can be used to broaden scientific understanding of the effects of LCS and health outcomes. These databases are underutilized, and they provide potential tools for grasping a fuller picture of LCS in the US diet.