The goal of this review was to critically evaluate the scientific evidence in humans on the potential effect of sweetened beverages on weight gain and risk of obesity in youth and adults. Two categories of these beverages were reviewed. Sugar-sweetened beverages (SSBs) include soft drinks, colas, other sweetened carbonated beverages, and fruit drinks with added sugar. Artificially sweetened beverages (ASBs), also referred to as non-nutritive sweetened beverages, are marketed and used as a replacement for SSBs for those who want to reduce sugar and caloric intake. The totality of evidence to date demonstrates a pattern across observational and experimental studies of an increased risk of weight gain and obesity with higher intake of SSBs. However, it remains difficult to establish the strength of the association and the independence from other potentially confounding factors. The primary reason for unclear conclusions regarding the robustness of any effect of SSBs is due to the heterogeneity and methodologic limitations of both observational and experimental studies on this topic. Although some observational studies have suggested that ASBs may cause increased risk of obesity and cardiometabolic diseases, there is no clear mechanism for this pathway, and the epidemiologic studies are highly inconsistent. An important issue with the observational studies on ASBs and obesity or disease risk is reverse causality bias, with higher-quality studies demonstrating this possibility. The field needs higher-quality experimental studies in humans, with relevant direct comparisons between sweetened beverages and their sweetened solid-food alternatives.