In view of neuroprotective effects of neurotrophins and neurotrophic factors on the damaged nervous tissue clinical attempts have been made to use these proteins in the treatment of neurodegenerative diseases. However, the attempts were unsuccessful. We discuss the main causes of this failure and outline a new clinical prospect due to the growing understanding of the mechanisms underlying neurotrophin activity in the nervous system. A special emphasis has been laid on advances in the research aimed at optimization of pharmacodynamics of neurotrophins, and at development of new delivery systems that would not only supplement the nervous system with required neurotrophins locally, but also regulate their quantity and time span of their delivery. An alternative method of physical exercise allowing to upregulate neurotrophins and their receptors is also discussed.