Free radicals are highly reactive and unstable chemical species with unpaired electrons in their atomic structures’ outermost shells. To become chemically stable, these highly reactive free radical species attack the major biological macromolecules of the body and cause structural and functional destruction to these compounds. The process of generating ROS and RNS, the two major classes of free radicals, is explored, indicating the chemical reactions that lead to the disbalance of antioxidants and prooxidants, resulting in oxidative stress in mammalian tissue. Moreover, this chapter will examine the link between oxidative stress and different acute and chronic pathological conditions, such as inflammation, hormonal diseases, cancer progression, ischemic reperfusion injury, neurodegenerative diseases, kidney diseases, gout, rheumatoid arthritis, and free radical-induced aging. It will also expound on the mechanisms by which free radicals cause different diseases.