Hearing loss is the most common form of sensorineural impairment, affecting 5.3% of the worldwide human population. Whereas 1 in 500 children is born with hearing disorders, sudden or progressive forms of hearing loss can appear at adult age. However, the physiological and molecular mechanisms involved in this pathological process remain unclear. Interestingly, an increasing number of studies have demonstrated that purinergic receptors could play a key role on hearing disorders and auditory pathway dysfunctions. This mini review summarizes the current data suggesting a key role of purinergic signaling in cochlear hair cell functions and their involvement in progressive hearing loss. Taken together, these studies provide new knowledge in the biochemical and physiological mechanism of purinergic receptors in cochlear cell functions and open the door for the development of new drugs candidates involved in hearing loss treatment.