Learning to read typically involves acquiring skills in print-to-sound decoding and text comprehension. These two processes are, however, so intertwined that their respective contributions to the cortical organization mediating reading are difficult to untangle. Here we first review dominant theories on the neural underpinnings of reading in typical hearing individuals, with a focus on the visual word form area (VWFA). We then discuss possible implications for individuals who have achieved literacy in the absence of auditory input, and possibly little-to-no use of spoken language. Which factors are likely to contribute to successful reading in this case? We then present a study that capitalizes on deaf and hearing populations with matched literacy skills to characterize the impact of print-to-sound knowledge versus reading comprehension on the functional organization of the occipito-temporal cortex, and in particular the VWFA. We present a critical review of how this work both aligns and departs from existing work, highlighting the many routes to changing brains so elegantly pioneered by Helen Neville.