In the mammalian cochlea, the two types of hair cells drastically differ in their anatomy and physiology. Each system receives a specific efferent control originating in the brainstem superior olivary complex. Inner hair cells are connected to the afferent type I ganglion neurons (comprising 95% of the auditory nerve) which postsynaptically receive the input of the lateral efferents. On the other hand, outer hair cells, whose electromotile properties are responsible for the active mechanism, are directly under medial efferent control. Neurochemically, both types of efferents are also well distinguished. The present paper reviews the efferent neurochemistry and pharmacology, with an emphasis on the protective roles of each system on cochlear function. The role of lateral efferent neurotransmitters such as enkephalins and dopamine in protecting the auditory nerve dendrites against excessive noise and/or excitotoxicity is especially addressed. The cholinergic medial efferents synapsing with the outer hair cells play a role in altering and/or modulating cochlear micromechanics. They could also be involved in a potentiating effect on aminoglycoside ototoxicity.