It is commonly accepted that inefficient recruitment and inadequate retention continue to threaten the completion of clinical trials intended to reduce the public health burden of neurological disease. This article will discuss the scientific, economic, and ethical implications of failure to recruit and retain adequate samples in clinical trials, including the consequences of failing to recruit adequately diverse samples. We will also discuss the more common challenges and barriers to efficient and effective recruitment and retention, and the impact these have on successful clinical trial planning. We will explain the newly established efforts within National Institute of Neurological Disorders and Stroke (NINDS) to monitor recruitment and retention with well-defined metrics and implementation of grant awards that include feasibility milestones for continued funding. Finally, we will describe our efforts to address some of the common challenges to recruitment and retention through assistance to investigators and coordinators with evidence-based support, tools, and resources for planning and strategizing recruitment and retention as well as a trans-NIH effort to improve awareness of clinical research in the general public.