Tricho-dento-osseous syndrome (TDO) is a rare autosomal dominant disorder with complete penetrance. Common clinical features include abnormalities of hair, teeth, and skull. Dental management of TDO patients is quite challenging in terms of existing dental and skeletal problems. The current article presents a 12-year-old girl suffering TDO, followed by a review on the published literature pertaining to the dental management of TDO patients. Patient history included, rejected corneal transplantation, stone-forming kidneys, and several previous dental treatments. She was noted to have signs of mandibular prognatia, frontal bossing of the skull, mild bilateral tibial bowing, microstomia, and labial fissures. Dental findings included severe generalized enamel defects, discolored teeth, microdontia, anterior open-bite, posterior cross-bite, deep periodontal pockets, hyperplastic inflamed gingiva, taurodontism of permanent molars, dental periapical radiolucencies, and missing teeth. She was the only child of healthy, nonconsanguineous parents with no familial history of similar congenital syndrome or dental abnormalities. A treatment plan was established based on medical/dental history and findings, using a team-based approach. This article emphasizes the importance of a multidisciplinary approach for the dental management of patients suffering TDO.