Obesity has recently emerged as a major global health problem. According to World Health Organization estimates, 1.6 billion adults worldwide were overweight (body mass index [BMI] 25 kg/m2) and at least 400 million were obese (BMI 30 kg/m2) in 2005, numbers that are expected to reach 2.3 billion and 700 million, respectively, by 2015. In the United States, the percentage of overweight and obese adults increased markedly from 47% and 15% in 1976 to 1980 to 66% and 33% in 2005 to 2006, with the greatest proportion of increase seen among non-Hispanic black and Mexican American women. 1, 2 The implications of excess body weight are far-reaching. Epidemiological studies indicate that overweight and obesity are important risk factors for type 2 diabetes mellitus (T2DM), cardiovascular disease, cancer, and premature death. 3 In the United States, healthcare expenditures attributable to overweight and obesity are estimated to be $147 billion or 9.1% of total healthcare costs per year. 4 Such excess costs could have serious repercussions for resource-poor countries, which must manage the dual burdens of chronic and infectious disease. In the setting of a pandemic of obesity and related chronic diseases, the American Heart Association recently released a scientific statement recommending reductions in added-sugar intake to no more than 100 to 150 kcal/d for most Americans. 5 The statement identified sugar-sweetened beverages (SSBs) as the primary source of added sugars in the American diet. 6 Although it has long been suspected that SSBs contribute at least in part to the obesity epidemic, only in recent years have large epidemiological studies been able to substantiate the relationship between SSB consumption and long-term weight gain, T2DM, and cardiovascular risk. It is thought that SSBs contribute to weight gain because of their high added-sugar content, low satiety, and potential incomplete compensation for total energy, leading to increased energy intake. 7, 8 In addition, because of their high amounts of rapidly absorbable carbohydrates such as various forms of sugar and high-fructose corn syrup (HFCS) and the large quantities consumed, SSBs may increase T2DM and cardiovascular risk independently of obesity as a contributor to a high dietary glycemic load (GL), leading to inflammation, insulin resistance, and impaired-cell function. 9 Fructose from any sugar or HFCS may also increase blood pressure and promote the accumulation of visceral adiposity, dyslipidemia, and ectopic fat deposition because of increased hepatic de novo lipogenesis. 10 Here, we review temporal patterns in SSB consumption and clinically relevant effects on obesity, T2DM, and cardiovascular disease risk, emphasizing potential underlying biological mechanisms, clinical implications, and consideration of methodological issues inherent in the literature.