Mycotoxins are contaminants of food and feed commodities worldwide and are considered an important risk factor for human and animal health. The molecular mechanisms behind the toxic effects of most mycotoxins are oxidative stress. Oxidative stress occurs when the formation of reactive oxygen species exceeds the capacity of the antioxidant defense. Oxidative stress augments lipid peroxidation, causes DNA damage, oxidative modification of proteins, thus damaging the biological membranes and leads ultimately to cell death. This review addresses the mechanism of oxidative stress, regulation and function of the three lines of antioxidant defense, and susceptibility of lipids, as main targets of oxidative damage, in connection with the effect of frequently occurring mycotoxins and multimycotoxin effects. It also summarizes the data associated with oxidative stress and membrane lipid damage based on the effect of fumonisin B1.