Rheumatoid arthritis (RA) is caused by oxidative stress, a biochemical process that negatively impacts cell growth, DNA, and cellular functions. The evidence in the cellular, molecular, and clinical domains strongly supports this theory. Several oxidative damage markers, including malondialdehyde (MDA), protein carbonyls, and DNA oxidation products (8-OHdG), are strongly associated with disease activity, treatment resistance, and progression of radiological imaging. It appears that OS is central to RA’s pathophysiology beyond its role as a secondary outcome of inflammation. It is important to note that OS also contributes to extra-articular manifestations of RA, such as atherosclerosis, one of the biggest causes of excess morbidity. According to Romero-Bueno, redox imbalances in RA are independently associated with premature vascular aging, proving that redox management could be integrated into cardiovascular risk reduction plans. Furthermore, researchers have found that oxidative stress may predict flare risk and drug response, further supporting its role in stratified care. There has been evidence that MDA and antioxidant enzyme levels fluctuate prior to changes in clinical scores, allowing for early therapeutic adjustments as discussed in this chapter.