Reactive oxygen species (ROS) are chemically reactive oxygen radicals or non-radical derivatives playing key role in various biochemical redox reactions. The presence of ROS within the “redox window” is beneficial as it is involved in different cell signaling pathways important for cell proliferation and apoptosis. However, deviation of ROS level from the “redox window” results in oxidative or reductive stress in the cellular mitochondria and have detrimental consequences. In the chapter we have discussed ROS generation, involvement in cell signaling pathways, and their extensive role in cancer progression and physiological ROS management in the treatment of cancer.