Congenital auditory deprivation (deafness) leads to a dysfunctional intrinsic cortical microcircuitry. This chapter reviews these deficits with a particular emphasis on layer-specific activity within the primary auditory cortex. Evidence for a delay in activation of supragranular layers and reduction in activity in infragranular layers is discussed. Such deficits indicate the incompetence of the primary auditory cortex to not only properly process thalamic input and generate output within the infragranular layers, but also incorporate top-down modulations from higher order auditory cortex into the processing within primary auditory cortex. Such deficits are the consequence of a misguided postnatal development. Maturation of primary auditory cortex in deaf animals shows evidence of a developmental delay and further alterations in gross synaptic currents, spread of activation, and morphology of local field potentials recorded at the cortical surface. Additionally, degenerative changes can be observed. When hearing is initiated early in life (e.g., by chronic cochlear-implant stimulation), many of these deficits are counterbalanced. However, plasticity of the auditory cortex decreases with increasing age, so that a sensitive period for plastic adaptation can be demonstrated within the second to sixth months of life in the deaf cat. Potential molecular mechanisms of the existence of sensitive period are discussed. Data from animal research may be compared to electroencephalographic data obtained from cochlear-implanted congenitally deaf children. After cochlear implantation in humans, three phases of plastic adaptation can be observed: a fast one, taking place within the first few weeks after implantation, showing no sensitive period; a slower one, taking place within the first months after implantation (a sensitive period up to 4 years of age); and possibly a third, and the longest one, related to increasing activation of higher order cortical areas.