This chapter provides an overview of the fundamentals of clinical trials in Alzheimer's disease (AD). A wide array of therapeutic interventions for AD is being developed. Clinical trials of the first approved treatments for AD have largely guided subsequent trials, though the targets, mechanisms of action, and intended indications of investigational treatments have evolved. Functional measures are included in nearly all clinical trials, and the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) is the most commonly used method to examine functional performance. Trial designs that theoretically confirm disease modification have been proposed, including the staggered start and randomized withdrawal designs. Demonstration of placebo group decline is critical to the effective testing of disease-modifying therapies. Finally, it is clear that AD biology begins prior to clinical phenomenology and this window of time may represent the ideal point of intervention.