Uric acid is an end-product of purine metabolism in humans. This is in contrast to most other mammals that express urate oxidase, an enzyme responsible for further metabolism of uric acid to allantoin. Consequently, humans have plasma uric acid levels approximately 10 times higher than most other mammals indicating biological significance of uric acid in man. Uric acid is the most abundant aqueous antioxidant, accounting for up to 60% of plasma antioxidative capacity. Although the chronic hyperuricemia is clearly associated with cardiovascular and renal diseases and metabolic syndrome, acute increase in plasma uric acid under different experimental conditions, even at high concentrations, did not cause detrimental cardiovascular effects in human subjects. In contrast, uric acid reduced exercise associated oxidative stress, protected endothelial function in patients with type 1 diabetes and regular smokers and against hyperoxia-induced oxidative stress and reduced the increase in arterial stiffness. Whereas, lowering serum urate did not improve endothelial function in patients with type 2 diabetes. On the other side, acute actions of established cardiovascular risk factors, such as high-fat meals, hyperhomocysteinemia, or cigarette smoking, cause immediate impairment of vascular function, in contrast to acutely increased plasma uric acid. Different mechanisms will be discussed in order to explain these paradoxical associations of uric acid, as well as pathophysiological conditions in which uric acid as an antioxidant may become pro-oxidant. Nonetheless, the role of uric acid as a causal, compensatory, or coincidental risk factor in cardiovascular system remains unclear.