Until recently, only five medicines have been approved for treatment of patients with Alzheimer’s disease (AD). Unfortunately, these agents offer just mild and temporary symptomatic improvement, without slowing progression of the disease itself. The Harrington Discovery Institute of University Hospitals Health System in Cleveland addresses this problem through a unique model that advances a diversified portfolio of new medicines for both treatment and prevention of AD. The institute identifies academic scientists in the USA, UK, and Canada who have made exceptionally innovative basic science discoveries related to AD and provides them with both financial support and critical programmatic direction. This latter contribution entails guidance and oversight from eminent drug developers whose collective expertise would normally only be available within a large pharmaceutical company. This enables academic scientists to bridge the “valley of death” between their scientific discoveries and development of medicines. As a result, HDI is bringing new medicines with novel mechanisms of action into the clinic for Alzheimer’s disease.