Noise-induced hearing loss remains one of the most prominent occupational diseases in Europe. However, noise is no longer perceived as the only source of work-related hearing damage and increasing attention is being paid to the risks of combined exposure to high-level noise and ototoxic substances, that is, those which can affect the structures and/or the function of the inner ear and the associated signal transmission pathways in the nervous system. This publication aims to provide an up-to-date picture of our knowledge in this field. It includes: a description of the basic features of the physiological mechanisms leading to hearing impairment, current diagnostic tools, and an overview of the chemicals that may be deleterious to the inner ear, ranking the certainty of their ototoxic properties in a defined weight-of-evidence approach. The review also identifies the health effects resulting from exposure to multiple ototoxic substances and also from the interaction of ototoxic substances and noise, pointing out the work areas where exposure to ototoxic substances is likely. Finally, the report highlights gaps in our current knowledge for proposed future action and research.