Noise-induced hearing loss (NIHL) means hearing loss or cochlear damage induced by either a short exposure to an intense impulse sounds from 100 to 150 dB SPL or continuous exposure to loud sounds at or above 85 dB SPL over relatively long period of time. Noise exposure results in oxidative stress destroying the antioxidant defense mechanism in the cochlea by over-production of reactive oxygen species (ROS), reactive nitrogen species (RNS), and other free radicals. The purpose of this study is to explain the basic mechanisms of NIHL and to review a target and the site of action of treatment in terms of free radical formation. Oxidative stress begins immediately after noise exposure and continues up to 21 days after the exposure. Cell death process progresses after noise exposure. A primary cell death pathway following noise exposure is called apoptosis. Pharmacological approaches for prevention or treatment of NIHL have been developed with both oxygen-based antioxidant drugs inhibiting the generation of ROS and nitrogen-based antioxidant drugs inhibiting the production of RNS. There are synergistic effects of combined antioxidant drugs because each antioxidant drug may target different treatment mechanism. When one antioxidant drug was used in combination with other antioxidant drugs, the amount of reduction was analyzed and described. In addition, the optimal timing of therapeutic effects of antioxidant drugs depends on the time of initial treatment and the length of treatment before and after noise exposure. The maximal effect of treatment was observed in treatment for 9 days with injection starting at 24 h after noise exposure. The treatment of antioxidant drugs extending up to 10 days after noise exposure can reduce cumulative cochlear damage resulting from the delayed formation of free radicals. However, the relationship between free radical formation and the optimal timing of treatment is still unclear. Further studies on the relationship should be continually performed because of clinical usefulness and its importance