Down syndrome (DS) is a genetic disorder that results from the triplication of chromosome 21. Accompanying this disorder are a number of medical conditions including intellectual disability and early- onset Alzheimer’s disease (AD). Our understanding of the molecular basis for these has expanded substantially in the past decade, both in patients and relevant animal models. In particular, exciting advances in therapies that modulate neurotransmitters to improve cognitive function have reached clinical trials. Moreover, increased insight into the pathogenesis of AD in DS has motivated clinical trials for AD in DS. Below, therapeutic strategies that have been deployed in clinical trials in DS will be discussed as well as their underlying scientific rational.