The endothelium is an important component of vascular homeostasis that is a target for injury in the setting of vascular disease. One means of promoting a maladaptive endothelial cell phenotype such as that seen in atherosclerosis is excess oxidative stress. Although this term once was almost exclusively used to describe low-density lipoprotein (LDL) and lipid oxidation in the vasculature, we now understand that the intracellular oxidant milieu is an important modulator of vascular cell function. Indeed, considerable data indicate that reactive oxygen species (ROS) are an important means of cellular signaling, although the precise mechanisms whereby ROS accomplish this are still under investigation. In this review, the data linking ROS to kinase activation and cell signaling in the endothelium is discussed, with a particular emphasis on the roles of protein thiol modification.