Alzheimer’s disease (AD) is growing in frequency rapidly and represents an area of urgent need in medical research. Now the sixth leading cause of death, AD is expected to triple in prevalence in coming decades. Key to averting the personal and international toll of AD will be clinical trials to examine the safety and efficacy of potentially disease-slowing therapies. These studies face a variety of challenges, including imperfect outcome measures, unvalidated surrogate biomarkers, and often slow and challenging recruitment. Nevertheless, a large number of promising potential therapies are in development. If successful and started early enough, these treatments could reduce the societal impact of AD. In this chapter, we provide an overview of the methodologies and designs of AD trials of potential disease-modifying therapies, the challenges these studies meet, and the targets and potential treatments that are currently in development.