VEGF is expressed in central nervous system and its expression increases in hypoxia and in inflammatory brain disorders. A wealth of data suggests that VEGF may exert neuroprotective activities and promote neuroregeneration in disease status. Moreover, the risk of developing certain neurological disorders may be dependent on dysfunction in the VEGF system. Therefore, a strong rationale does exist to suggest that VEGF-based therapeutics could be implemented in conditions such as stroke or amyotrophic lateral sclerosis and experimental data supporting this hypothesis have been obtained. However, the unfavorable pharmacokinetic profile of this growth factor, and concerns on its safety have limited the development of VEGF as a therapeutic tool for neurological disorders. In this review, we discuss why a new class of VEGF-mimic peptides holds promises to become a safer, cheaper and more easily manageable tool for central nervous system therapeutics. Focal Points ● Bench: The analysis of the effects of small peptides reproducing one or more regions of VEGF may help understanding basic issues on the structure-activity relationship of this growth factor. ● Bedside: Small VEGF-mimic peptides could have better pharmacokinetic and/or toxicological properties than VEGF and be, therefore, potentially suitable for use in human diseases. ● Community: VEGF-mimic peptides-based therapeutics could help reducing the burden of severe neurodegenerative disorders that cannot be efficiently treated with currently available drugs.