Despite high enthusiasm, early attempts to develop clinical treatments based on animal research with neurotrophins were not successful. Here we survey clinical trials with neurotrophins, compared with neurotrophic factors of other gene families, and delineate the most likely reasons for their failure. We then suggest improved methods for regulated local supply of NTs to specific populations of neurons and discuss future therapeutic procedures evolving from the more detailed knowledge of the signal transduction pathways activated by neurotrophins via their receptors.