The growing global focus on the adverse health conditions associated with excessive sugar consumption has prompted health and policy organizations as well as the public to take a more mindful approach to health and wellness. In response, food and beverage companies have proactively innovated and reformulated their product portfolios to incorporate low and no-calorie sweeteners (LNCSs) as viable alternatives to sugar. LNCSs offer an effective and safe approach to delivering sweetness to foods and beverages and reducing calories and sugar intake while contributing to the enjoyment of eating. The objective of this paper is to enhance the understanding of LNCSs segmentation and definitions, dietary consumption and reduction guidance, front-of-package labeling, taste and sensory perception and physiology, metabolic efficacy and impact, as well as the overall safety of LNCSs and sugar.