|Oxidative stress is a fundamental principle in the pathophysiology of many diseases. It occurs when the production of reactive oxygen species exceeds the capacity of the cell defense system. The hydroxyl radical is a reactive oxygen species that is commonly formed in vivo and can cause serious damage to biomolecules, such as lipids, proteins, and nucleic acids. It plays a role in inflammation-related diseases, like chronic inflammation, neurodegeneration, and cancer. To overcome excessive oxidative stress and thus to prevent or stop the progression of diseases connected to it, scientists try to combat oxidative stress and to find antioxidant molecules, including those that scavenge hydroxyl radical or diminish its production in inflamed tissues. This article reviews various methods of hydroxyl radical production and scavenging. Further, flavonoids, as natural plant antioxidants and essential component of the human diet, are reviewed as compounds interacting with the production of hydroxyl radicals. The relationship between hydroxyl radical scavenging and the structure of the flavonoids is discussed. The structural elements of the flavonoid molecule most important for hydroxyl radical scavenging are hydroxylation of ring B and a C2-C3 double bond connected with a C-3 hydroxyl group and a C-4 carbonyl group. Hydroxylation of ring A also enhances the activity, as does the presence of gallate and galactouronate moieties as substituents on the flavonoid skeleton.