UNLABELLED: Hypodontia is an inherited condition involving the absence of one to six teeth. The permanent dentition is the most frequently affected; however, it may also affect the primary dentition. A congenitally missing tooth (CMT) is the most common dental abnormality, with the missing mandibular second premolar, maxillary lateral incisor, maxillary second premolar, and mandibular central incisor accounting for 90% of CMT in hypodontia studies. The etiology of CMT has been attributed to environmental and genetic contributing factors, with the latter having a strong influence. It may occur in isolation or in association with syndromes. Congenitally missing mandibular incisor is more common in the Asian population and females. Depending on the number and location of missing teeth, hypodontia may be a considerable issue for the clinician since it may impact occlusal balance, mastication, speech, and esthetics and often requires a multidisciplinary approach. Missing mandibular incisors are of particular interest to orthodontists because of the possibility of mandibular retrognathism, the potential for the development of malocclusion, and difficulty in achieving a balanced occlusion. This case report describes the skeletal and dental features of a nonsyndromic familial occurrence of missing mandibular incisors in three generations. A comprehensive literature search was also performed to review the familial cases with missing mandibular incisors. HOW TO CITE THIS ARTICLE: Selvaraj M, Sennimalai K, Samrit VD, A Rare Incidence of Nonsyndromic Mandibular Incisor Agenesis in a Three-generation Family: Case Report and Literature Review. Int J Clin Pediatr Dent 2023;16(2):388-395.