Down syndrome is the most common genetic cause of mental retardation and one of the most frequently occurring neurodevelopmental genetic disorders in children. Children with Down syndrome typically experience a constellation of symptomology that includes developmental motor and language delay, specific deficits in verbal memory, and broad cognitive deficits. Children with Down syndrome are also at increased risk of medical problems, which can exacerbate their cognitive deficits. Although the diagnosis of Down syndrome is facilitated by cytogenetic testing and the unique physical phenotype, the development of proper interventions for this group of children is less obvious. Despite their functional deficits, children with Down syndrome possess relative strengths, which can be the focus of interventions. This article reviews the etiology and developmental course of Down syndrome, appraises examples of empirically validated interventions, and discusses neurocognitive processing issues that should be considered during a psychoeducational evaluation for intervention.