© Oxford University Press 2014. All rights reserved. Until recent years, the prevailing view had been that the central nervous system of the adult mammal was incapable of enduringly changing in either its physiology or structure in reaction to environmental forces that had conditioned long-lasting changes in behaviour, i.e., during learning. One unfortunate consequence was that clinicians were discouraged from viewing rehabilitation for neurological illness optimistically or even designing controlled experimental trials to challenge the prevailing view. Nonetheless, scientific evidence in support of use-dependent neuroplasticity in adults gradually accrued over the past century. This chapter charts major historical forces against neuroplasticity and avenues of research that ultimately led to the current renaissance of appreciation for the occurrence of adult neuroplasticity in health and disease.