Whereas individuals with Down syndrome maintain relatively high levels of social intelligence and procedural learning, they often suffer from grossly impaired declarative or explicit memory. Not surprisingly, brain structures associated with declarative memory, namely the hippocampal and parahippocampal regions of the medial temporal lobe, are the most severely affected in persons with Down syndrome. The nature of these deficits suggests that therapies targeting hippocampal function would be particularly efficacious in ameliorating the cognitive deficits seen in persons with Down syndrome and, consequently, would enhance their quality of life.