Diabetes and cardiovascular disease have emerged as major threats to human health, and the risk of developing these chronic conditions is increased in individuals with abdominal obesity and the metabolic syndrome. Excess visceral abdominal tissue (VAT) accumulation appears to be a key feature of abdominal obesity contributing to the development of the metabolic syndrome. For instance, excess VAT is accompanied by elevated triglycerides, reduced high-density lipoprotein (HDL) cholesterol, elevated blood pressure, and/or elevated fasting plasma glucose. In addition, the rather normal or only marginally elevated low-density lipoprotein (LDL) cholesterol concentrations in patients with excess VAT could provide misleading information as viscerally obese patients have an increased plasma concentration of small, dense LDL particles. Prospective studies have suggested that even among patients with LDL cholesterol concentrations within normal limits, an increased concentration of small LDL particles is associated with higher risk of cardiovascular disease. With the treatment of abdominal obesity and excess VAT, an increase in patients' LDL particle size and improvements in other cardiovascular risk factors (eg, insulin levels, glucose tolerance, HDL, C-reactive protein [CRP], and adiponectin levels) can be achieved. Waist circumference can be used in clinical practice as a first approach and as a crude index to identify patients who have excess VAT, particularly when the elevated waistline is accompanied by the clinical features of the metabolic syndrome, among which an elevated fasting triglyceride concentration appears to be predictive of a reduced LDL particle size and of further metabolic abnormalities frequently referred to as the metabolic syndrome. Lifestyle changes, including more physical activity and healthier nutritional habits, are the cornerstone of therapy for high-risk abdominally obese patients with an excess of VAT. In addition, results from the RIO-Lipids study, which was conducted in high-risk obese, dyslipidemic patients, have provided evidence that CB1 receptor blockade with rimonabant can induce significant weight loss, and, more importantly, improve the cardiometabolic risk profile beyond what could be explained by the weight loss effects of the drug.