In recent years, there has been episodic speculation that an increase in consumption of fructose from foods and beverages is an underlying factor responsible for the relatively recent increase in obesity and obesity-related diseases such as diabetes. Reports in support of this hypothesis have been published, showing that concentrations of triglycerides (TG) are higher and concentrations of insulin and hormones associated with satiety are lower in animals following the ingestion of fairly large quantities of fructose, compared to other carbohydrates. However, results from human studies are inconsistent. A possible reason for the inconsistent results is that they are dependent on the particular study population, the design of the studies, and/or the amount of fructose administered. A systematic assessment of the strength and quality of the studies and their relevance for healthy, normal weight humans ingesting fructose in a normal dietary manner has not been performed. The purpose of this review was to critically evaluate the existing database for a causal relationship between the ingestion of fructose in a normal, dietary manner and the development of hyperlipidemia or increased body weight in healthy, normal weight humans, using an evidence-based approach. The results of the analysis indicate that fructose does not cause biologically relevant changes in TG or body weight when consumed at levels approaching 95th percentile estimates of intake.