General use and popularity of over-the-counter supplemental antioxidants have rapidly spread all over the world and are believed to promote cardiovascular health and wellbeing. However, there is a paucity of information and lack of proof that physiological and above-physiological levels of oxidants do harm at the cellular and organismal levels. Instead, several reports demonstrated that reduction in Reactive Oxygen Species (ROS) did not improve vascular function. Interestingly, recent studies show that increased ROS levels play protective role in vascular endothelium and may improve coronary endothelial function. In the current review, we introduce the concept that increased ROS levels, often seen in association with cardiovascular disease, probably is an endothelial-way or ‘oxidative response’ to cope with vascular pathology.