Millions of people worldwide are exposed to harmful levels of noise daily in their work and leisure environment. This makes noise-induced hearing loss (NIHL) a major occupational health risk globally. NIHL is the second most common form of acquired hearing loss after age-related hearing loss and is itself a major contributing factor to presbycusis. Temporary threshold shifts, once thought to be relatively harmless and recoverable, are now known to cause permanent cochlear injury leading to permanent loss of hearing sensitivity. This article reviews the current understanding of the cellular and molecular pathophysiology of NIHL with latest findings from animal models. Therapeutic approaches to protect against or to mitigate NIHL are discussed based on their proposed action against these known mechanisms of cochlear injury. Successes in identifying genes that predispose individuals to NIHL by candidate gene association studies are discussed with matched gene knockout animal models. This links to exciting developments in experimental gene therapy to replace and regenerate lost hair cells and post-noise otoprotective therapies currently being investigated in clinical trials. The aim is to provide new insights into current and projected future strategies to manage NIHL; bench to bedside treatment is foreseeable in the next 5 to 10 years.