Naturally occurring stimuli can vary over several orders of magnitude and may exceed the dynamic range of sensory neurons. As a result, sensory systems adapt their sensitivity by changing their responsiveness or ‘gain’. While many peripheral adaptation processes are rapid, slow adaptation processes have been observed in response to sensory deprivation or elevated stimulation. This adaptation process alters neural gain in order to adjust the basic operating point of sensory processing. In the auditory system, abnormally high neural gain may result in higher spontaneous and/or stimulus-evoked neural firing rates, and this may have the unintended consequence as presenting as tinnitus and/or sound intolerance, respectively. Therefore, a better understanding of neural gain, in health and disease, may lead to more effective treatments for these aberrant auditory perceptions. This review provides a concise summary of: (i) evidence for changes in neural gain in the auditory system of animals, (ii) physiological and perceptual changes in adult human listeners following an acute period of enhanced acoustic stimulation and/or deprivation, (iii) physiological evidence of excessive neural gain in tinnitus and hyperacusis patients, and (iv) the relevance of neural gain in the clinical treatment of tinnitus and hyperacusis.