Fleisher et alArticle study the safety, tolerability, and amyloid β response to a γ-secretase inhibitor (LY450139) in Alzheimer disease. The clinical trial provides promising results, as LY450139 was generally well tolerated at doses of up to 140 mg taken daily for 14 weeks, with several findings indicating the need for close clinical monitoring in future studies. Decreases in plasma amyloid β concentrations were consistent with inhibition of γ-secretase. Clearly, a larger study group, neuropsychological testing, magnetic resonance imaging evaluations, and a longitudinal follow-up are required to determine its clinical effectiveness to alter the course of the disease in a meaningful manner. This study offers important new data for planning future studies.