Several factors have been studied in an effort to explain why the prevalence and degree of noise-induced hearing loss (NIHL) can vary so much within a group and among groups. Some of the factors studied to date include variations in exposure (see Henderson and Hamernik, Chap. 4), age (see Rabinowitz, Chap. 2; Bielefeld, Chap. 10), gender, genetics (see Gong and Lomax, Chap. 9), race, and general health indicators, such as blood pressure and use of certain medications (Toppila et al. 2000). The focus of the present chapter is the interaction of ototoxic industrial chemicals with noise, which results in increased hearing loss. Hearing loss can occur after ingestion of certain drugs due to their effects on the peripheral auditory system or central nervous system. The mechanisms of action of ototoxic substances may involve the entire organ, specific cells within the organ, components of specific cells, or individual biochemical pathways. Drugs and other substances that alter hearing or equilibrium by acting primarily at the level of the brain stem or the central auditory pathways are considered to be neurotoxic and not strictly ototoxic (Hawkins 1976). The ototoxicity of therapeutic drugs has been recognized since the nineteenth century. Schacht and Hawkins (2006) reviewed initial reports that associated the intake of certain drugs such as quinine and acetylsalicylic acid with temporary hearing loss as well as dizziness and tinnitus. In the 1940s, permanent damage to the cochlea was reported in several patients treated with the newly discovered drug for treatment of tuberculosis, the aminoglycoside antibiotic streptomycin (Hinshaw and Feldman 1945). Today there are many well known ototoxic drugs used in clinical situations. Most of them (antibiotics, chemotherapeutics, diuretics, and antimalaria drugs) are used despite these negative side effects to treat other serious, sometimes life-threatening conditions. In the developed nations, and in some developing ones, the prescription of these drugs will trigger "ototoxicity monitoring" of patients to allow early detection of auditory effects and, when necessary, audiologic interventions to address the hearing impairment (AAA 2009). In contrast, only in the past 20 years has the ototoxicity of chemicals found in the environment from contaminants in air, food or water, and in the workplace become a concern for researchers, toxicologists, audiologists, and other healthcare professionals. Initial reports described the ototoxicity of environmental chemicals after acute intoxications or poisonings, and these reports included observations that hearing loss was more common and sometimes more severe in work settings where chemical exposures occurred (Barregard and Axelsson 1984). Since then, considerable progress toward understanding the effects of certain environmental and occupational chemicals on the auditory system and their interactions with noise has been made (Fechter et al. 1987; Morata 1989; Lataye et al. 2000). Today, ototoxic properties have been identified for multiple classes of industrial chemicals, including solvents, metals, asphyxiants, pesticides, and polychlorinated biphenyls (PCBs). The rest of this chapter reviews the ototoxicity of these compounds and their interactions with noise. Ototoxicants are of interest in the work environment, not only because of their actions on the hearing system of humans, but also because they may interact with each other and with noise when exposure is combined (simultaneously or sequentially). It is well known that the effects of many drugs or agents, when given concurrently, cannot necessarily be predicted on the basis of their individual effects. In such instances, the damage incurred by agents acting together may exceed the simple summation of the damage each agent produces alone (Prosen and Stebbins 1980; Humes 1984). This synergistic effect is separate from, and perhaps more dangerous than, simple additive effects, as these synergistic effects are difficult to predict. Because noise is the most common exposure that causes hearing loss in humans, special attention has been given to the combined exposure to noise and agents with ototoxic effects on the auditory system. Solvents and carbon monoxide are the environmental/occupational chemicals most extensively studied to date because of their ubiquitous industrial use. These are chemicals that are widely used in several industrial sectors. Studies conducted with animal subjects have shown that some solvents can reach the inner ear through the blood stream even before they are metabolized. Solvents were found in the endolymph and perilymph, and these solvents not only caused damage to some inner ear structures, but also impaired auditory function (Campo et al. 1999). The onset, site, mechanism, and extent of ototoxic damage of these toxicants vary according to risk factors that include type of chemical, level and duration of chemical exposure, interactions between chemicals or noise, noise exposure level, and duration. Dose-response properties have not been precisely identified, but it appears that risk increases with increasing exposure, as is the case with ototoxic drugs such as cisplatin (used in chemotherapy) and aminoglycoside antibiotics (Laurell and Jungelius 1990; Halsey et al. 2005). Ototoxic drugs often cause a high-frequency hearing loss whereas the hearing loss caused by occupational exposure to chemicals can be very similar to a hearing loss caused by excessive noise. Because noise exposure is so common in modern societies, this might explain the delay in recognizing the risk to hearing that these chemicals can pose. Pure-tone audiometry, the standard clinical test used to determine a person's hearing sensitivity at specific frequencies, offers little information as to the relative health of inner (IHCs) and outer hair cells (OHCs), and the neural population. In other words, pure-tone audiometry does not provide information on the cause of the hearing loss. Other hearing tests such as word recognition, auditory reflex, and otoacoustic emission tests can help identify the site of damage. This information may help to differentiate the effects of chemicals from the effects of noise, as chemicals can affect more central portions of the auditory system (Ödkvist et al. 1987; Möller et al. 1989). In the presence of central deficits not only will sounds be perceived as less loud, but they may also be perceived as distorted.