Kraepelin originally defined dementia praecox as a progressive brain disease, although this concept has received various degrees of acceptance and rejection over the years since his famous published textbooks appeared. This article places an historical perspective on the current renewal of Kraepelin's concept in brain imaging literature that supports progressive brain change in schizophrenia from its earliest stages through its chronic course. It is concluded that a great deal of future research is needed focusing on the longitudinal course of change, the extent to the regions of change within each individual and the underlying mechanism and implications of brain change through functional and neurochemical imaging, combined with structural studies in the same individuals.