Sound localization is a computational process accomplished along the auditory pathway. Once the acoustic information received at each ear is analyzed independently (monaural cues) and comparatively (binaural cues), those cues are integrated to generate a coherent spatial percept. Using adult ferrets trained by positive conditioning in a spatial task, we aimed to study the role of the auditory cortex in the ability to localize sounds under both normal hearing and monaurally occluded conditions, the latter of which requires a reinterpretation of the values of the localization cues. Sound localization deficits were found after lesion or inactivation of the different auditory cortical regions, thereby indicating their participation in spatial processing. The differential impairments found in the approach-to-target and in the head movement responses reveal the complex relationship between cortex and midbrain which are putatively responsible for the voluntary and reflexive aspects of localization behaviour respectively. Furthermore, every auditory cortical region contributes to the adaptation process that follows monaural occlusion, indicating the key role that the auditory cortex plays in experience-dependent plasticity. Also, the selective lesion of the descending projections from the auditory cortex to the inferior colliculus by chromophore-targeted laser photolysis has revealed the essential function that descending pathways play in learning-induced localization plasticity.