The inferior colliculus (IC) receives prominent projections from centralized neuromodulatory systems. These systems include extra-auditory clusters of cholinergic, dopaminergic, noradrenergic, and serotonergic neurons. Although these modulatory sites are not explicitly part of the auditory system, they receive projections from primary auditory regions and are responsive to acoustic stimuli. This bidirectional influence suggests the existence of auditory-modulatory feedback loops. A characteristic of neuromodulatory centers is that they integrate inputs from anatomically widespread and functionally diverse sets of brain regions. This connectivity gives neuromodulatory systems the potential to import information into the auditory system on situational variables that accompany acoustic stimuli, such as context, internal state, or experience. Once released, neuromodulators functionally reconfigure auditory circuitry through a variety of receptors expressed by auditory neurons. In addition to shaping ascending auditory information, neuromodulation within the IC influences behaviors that arise subcortically, such as prepulse inhibition of the startle response. Neuromodulatory systems therefore provide a route for integrative behavioral information to access auditory processing from its earliest levels.