This review aimed to investigate the use of the Cambridge Neuropsychological Automated Testing Battery (CANTAB) for people at risk of cognitive impairment, especially those born with Down syndrome and those born preterm. Six databases were searched according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards, in addition to the bibliography index listed in the CANTAB site. Twenty four studies regarding Down syndrome and 17 regarding prematurity were reviewed and are here described. Both cognitive profiles were described, and their performance was compared on specific tasks and CANTAB tests. In this battery of tests, people with Down syndrome usually present impaired key cognitive domains, such as episodic memory and recognition memory. Results were presented considering general aspects described in the studies, specific findings such as dementia, the role of genetics, and cognitive profile, among other descriptions. Comparability between both populations in future studies is discussed.