The generation of reactive oxygen species (ROS) and other free radicals (R) during metabolism is a necessary and normal process that ideally is compensated for by an elaborate endogenous antioxidant system. However, due to many environmental, lifestyle, and pathological situations, excess radicals can accumulate, resulting in oxidative stress. Oxidative stress has been related to cardiovascular disease, cancer, and other chronic diseases that account for a major portion of deaths today. Antioxidants are compounds that hinder the oxidative processes and thereby delay or prevent oxidative stress. This article examines the process of oxidative stress and the pathways by which it relates to many chronic diseases. We also discuss the role that endogenous and exogenous antioxidants may play in controlling oxidation and review the evidence of their roles in preventing disease.