Various topical preparations are widely used for treating external otitis, acute otitis media with perforation, post-tympanostomy tube otorrhea, and chronic suppurative otitis media. Solutions and suspensions that enter the middle ear through a perforated tympanic membrane can reach the inner ear by crossing through the round window membrane. The safety of various components of otic solutions used in this way, particularly aminoglycosides, corticosteroids, solvents, and preservatives, has been questioned in light of their ototoxic potential. The authors' objective is to review the literature discussing the safety of commonly used classes of otic preparations in settings in which the constituents can access the middle and inner ear in high concentrations and discuss their clinical experience with ototoxicity and experience with medical-legal issues.