Noise-induced hearing loss (NIHL) is a common injury for service members and civilians. Effective prevention of NIHL with drug agents would reduce the prevalence of NIHL. There are a host of challenges in translation of investigational new drug agents from animals into human clinical testing, however. Initial articles in this special issue describe common pre-clinical (animal) testing paradigms used to assess potential otoprotective drug agents and design-related factors that impact translation of promising agents into human clinical trials. Additional articles describe populations in which NIHL has a high incidence and factors that affect individual vulnerability. While otoprotective drugs will ultimately be developed for use by specific noise-exposed populations, there has been little effort to develop pre-clinical (animal) models that accurately model exposure hazards across diverse human populations. To facilitate advances in the translational framework for NIHL otoprotection in pre-clinical and clinical testing, the overarching goals of the current series are to (1) review the animal models that have been used, highlighting the relevance to the human populations of interest, (2) provide insight into the populations for whom pharmaceutical interventions might, or might not, be appropriate, and (3) highlight the factors that drive the significant individual variability observed in humans.