The study aimed at exploring the effectiveness of cognitive intervention with the new ‘‘Instrumental Enrichment Basic’’ program (IE-basic), based on Feuerstein’s theory of structural cognitive modifiability that contends that a child’s cognitive functioning can be significantly modified through mediated learning intervention. The IE-basic program is aimed at enhancing domain-general cognitive functioning in a number of areas (systematic perception, self-regulation abilities, conceptual vocabulary, planning, decoding emotions and social relations) as well as transferring learnt principles to daily life domains. Participants were children with DCD, CP, and intellectual impairment of genetic origin, autistic spectrum disorder, ADHD or other learning disorders, with a mental age of 5–7 years, from Canada, Chile, Belgium, Italy and Israel. Children in the experimental groups (N = 104) received 27–90 h of the program during 30–45 weeks; the comparison groups (N = 72) received general occupational and sensory–motor therapy. Analysis of the pre- to post-test gain scores demonstrated significant (p < 0.05) advantage of experimental over comparison groups in three WISC-R subtests (‘‘Similarities’’, ‘‘Picture Completion’’, ‘‘Picture Arrangement’’) and Raven Coloured Matrices. Effect sizes ranged from 0.3 to 0.52. Results suggest that it is possible to improve cognitive functioning of children with developmental disability. No advantage was found for children with specific etiology. Greater cognitive gains were demonstrated by children who received the program in an educational context where all teachers were committed to the principles of mediated learning.