Accelerating the pace of development for neuroprotective agents requires a number of advances in the therapeutics of Alzheimer disease. Identification of patients who are presymptomatic, by discovering early markers of Alzheimer disease will be essential. Clinical trials methodology must be devised to accommodate atypical outcome measures, prolonged trials, and large sample sizes without posing serious ethical considerations regarding placebo administration. Finally, regulatory issues that discourage development of drugs that will be in complicated expensive and lengthy clinical trials need to be addressed. This paper reviews these issues, and offers some suggestions.