Neurotrophic factors play a major role in brain development and function. Because administration of these factors can attenuate degeneration of neurons and behavioral deficits in animals, such molecules may become useful in the treatment of AD. At the present time, a solid rationale can be made for clinical trials with NGF, given the pronounced trophic effect of NGF on forebrain cholinergic neurons and the cholinergic atrophy occurring in AD. Future research in the following areas will be crucial toward development of successful neurotrophic factor therapy: (a) New research should focus on identifying new neurotrophic factors, which protect other vulnerable neurons in AD, in particular hippocampal and cortical neurons; (b) Multiple available strategies should be pursued to find ways to deliver neurotrophic proteins across the blood-brain barrier. In addition, a broadly based effort to establish a small-molecule pharmacology of neurotrophic factors is likely to lead to clinically useful drugs; (c) Regulatory guidance is necessary to establish ethically acceptable designs for clinical trials to unequivocally establish efficacy of drugs that attenuate the progression of AD.