This chapter describes the significance of oxidative stress and its involvement in major oral and general diseases, and discusses damage inflicted by oxidative stress to cellular structures. Atmospheric oxygen presents two unpaired electrons in the outer electron shell. Oxygen reduction takes place in a sequential addition of electrons that leads to reactive oxygen species (ROS) formation among which are superoxide, hydrogen peroxide, and hydroxyl radical. There is solid evidence that many oral diseases such as periodontitis or oral cancer are directly linked to loss of balance between antioxidant systems and endogenous or exogenous prooxidants. Moreover, oxidative stress is directly associated with several general pathological conditions, and in many cases, it represents the systemic link between the initiation of general diseases and the development of various oral conditions. These observations thoroughly justify the continuous search for new antioxidants as well as antioxidant usage in the prophylaxis and treatment of oral diseases.