The developing mammalian cerebral cortex contains a distinct class of cells, subplate neurons (SPns), that play an important role during early development. SPns are the first neurons to be generated in the cerebral cortex, they reside in the cortical white matter, and they are the first to mature physiologically. SPns receive thalamic and neuromodulatory inputs and project into the developing cortical plate, mostly to layer 4. Thus SPns form one of the first functional cortical circuits and are required to relay early oscillatory activity into the developing cortical plate. Pathophysiological impairment or removal of SPns profoundly affects functional cortical development. SPn removal in visual cortex prevents the maturation of thalamocortical synapses, the maturation of inhibition in layer 4, the development of orientation selective responses and the formation of ocular dominance columns. SPn removal also alters ocular dominance plasticity during the critical period. Therefore, SPns are a key regulator of cortical development and plasticity. SPns are vulnerable to injury during prenatal stages and might provide a crucial link between brain injury in development and later cognitive malfunction.