A number of congenital conditions include oxidative stress as a phenotypic hallmark, in spite of very distinct genotypic assets. These disorders include some rare chromosomal instability syndromes and two frequent congenital conditions, Down's syndrome and cystic fibrosis. All of these disorders generate severe biomedical and social handicaps in their progression, resulting in neurological symptoms or malformations, early ageing and cancer proneness. The onset of oxidative stress has been related to excess formation or defective detoxification of reactive oxygen species. Investigations conducted so far have focussed on individual disorders and have utilised a range of different methodologies, so leading to a number of unanswered questions regarding the role(s) for oxidative stress in these disorders. Comparative studies are required, based on homogeneous methods, to provide insights into the pathogenesis of each individual condition, which may open up new avenues for studying ageing and cancer.