Through understanding the underlying mechanisms of noise-induced hearing loss (NIHL), several promising pharmacologic otoprotective agents are in development. Conversely, the experimental results with these protective agents further elucidate NIHL mechanisms. This article reviews the major classes of otoprotective agents for NIHL that have undergone published peer reviewed clinical trials, or are currently in or approaching FDA approved clinical trials. Both prophylactic and rescue agents are included. The classes of agents include antioxidants, vasodilators, and glucocorticoids. Apoptotic pathway inhibitors are briefly mentioned. For antioxidants, some of the differences in the exact antioxidant mechanisms are included. Protective agents reviewed include D-methionine, N-acetylcysteine, ebselen, ACE Mg, Acuval, CoQ10, molecular hydrogen, magnesium as a single agent, and dexamethasone. The advantages, disadvantages, and state of development are included for each agent. Both safety and efficacy are considered as are considerations for specific patient populations if known. Further, results of animal and clinical trials are briefly described from the published literature.