Lead-induced oxidative stress contributes to the pathogenesis of lead poisoning for disrupting the delicate prooxidant/antioxidant balance that exists within mammalian cells. Production of reactive oxygen species (ROS) is increased after lead treatment in in vitro studies. In vivo studies suggest that lead exposure causes generation of ROS and alteration of antioxidant defense systems in animals and occupationally exposed workers. The mechanisms for lead-induced oxidative stress include the effect of lead on membrane, DNA, and antioxidant defense systems of cells. From low to high doses of lead exposure, there are different responses of lead-induced oxidative stress in various target sites including lung, blood vessels, testes, sperm, liver, and brain in epidemiological as well as animal studies. Therefore, reducing the possibility of lead interacting with critical biomolecules and inducing oxidative damage, or bolstering the cell's antioxidant defenses might be associated with the beneficial role of antioxidant nutrients through exogenous supplementation of antioxidant molecules. Although many researchers have investigated the benefit of antioxidants in preventing lead toxicity, the mechanisms of antioxidant nutrients being effective via rebalancing the impaired prooxidant/antioxidant ratio are not completely clear. Antioxidant nutrients including, vitamin E, vitamin C, vitamin B(6), beta-carotene, zinc, and selenium, are addressed in this review to discuss their beneficial role in lead-induced oxidative stress.