Among the key challenges in Alzheimer’s disease drug development is the timely completion of clinical trials. Unfortunately, clinical trials often suffer from slow or insufficient enrollment. Successful clinical trial recruitment describes a balance between expeditiously achieving full enrollment and ensuring an appropriate study sample. Investigators face a number of challenges to the successful negotiation of this balance. The failure to address these challenges means that drug development may take more time and money and that trial results may not adequately represent drug efficacy or may not be applicable beyond the study. We review the challenges to recruitment and retention in Alzheimer’s disease clinical trials and present a framework to address them.