Loss of cochlear hair cells leads to permanent hearing loss. Hair cells may degenerate due to hereditary or environmental causes, or a combination of the two. Cochlear supporting cells actively participate in the process of hair cell elimination and scar formation by rapidly expanding and sealing the reticular lamina, the barrier between endolymph and perilymph. This scarring process helps preserve the remaining hair cells and hearing. Anti-apoptotic agents, anti-oxidants and several growth factors have been shown to protect hair cells and hearing against environmental insults. Characterization of the genes that regulate the development of the inner ear and its response to trauma has been helpful in designing strategies for enhancing protection of the inner ear and for inducing hair cell regeneration. This chapter discusses the potential for some of these approaches.