The mismatch negativity (MMN) is an automatic cortical evoked potential that signifies the brain's detection of acoustic change. In other words, the MMN reflects the neurophysiologic processes that underlie auditory discrimination. As such, the MMN provides an objective tool for evaluating central auditory mechanisms involved in speech perception.We are using the MMN to study the central auditory processes that encode acoustic changes important for speech perception in 1) normal-hearing adults and children, 2) individuals with impaired auditory systems (including persons with learning disabilities, attention deficit disorders, cochlear implants), and 3) an animal model. Specifically, we have demonstrated that the MMN provides information about the central processing of fine acoustic differences, the neuroanatomic pathways that encode acoustic change, central auditory processing in the presence of peripheral hearing deficits, and central auditory system plasticity, In addition, we have considered methodological challenges associated with measuring the MMN in individual subjects. Several methodological issues—including appropriate stimuli, stimulus presentation variables, the recording protocol and environment, and validation of the MMN in individuals—are discussed.