Asthma and allergic diseases have become a worldwide public health concern because of their increased prevalence. Despite decades of research on risk factors, the causes of these disorders are poorly understood. They are thought to develop through complex interactions between genetic and environmental factors. Because pulmonary and systemic oxidative stress increase inflammatory responses relevant to asthma and allergy, dietary or vitamin supplementation with antioxidants (a broad and varied category) has been proposed as an approach to reducing asthma incidence or morbidity. Meta-analyses of observational epidemiologic studies of variable methodological quality suggest associations of relatively low dietary intake of antioxidants and higher asthma and allergy prevalence. However, there have been few longitudinal studies of maternal or child dietary or vitamin/supplement antioxidant intake and asthma/allergy development. Moreover, there are no clinical trial data to support the use of dietary antioxidants or supplements to prevent asthma or allergy. A few small clinical trials suggest that specific antioxidants from diet or vitamin supplements might improve asthma control or lung function in asthmatic children or adults. Studies suggest that responses to antioxidants might be modified by life stage, genetic susceptibility, and environmental sources of oxidative stress. Large trials of antioxidant vitamin supplementation to prevent cancer suggest an increase in overall mortality with antioxidant vitamin supplementation, at least in populations with sufficient dietary antioxidant intake. This cautionary experience suggests that future trials to assess whether antioxidants reduce asthma incidence or improve asthma control should focus on supplementation of dietary sources of antioxidants. The potential benefits and risks of trials of vitamin supplements might be considered in special situations in which vulnerable populations have marked deficiency in dietary antioxidants, poor access to dietary antioxidants, and high exposure to environmental sources of oxidants.