Hypodontia, or tooth agenesis, is the most prevalent craniofacial malformation in humans. It may occur as part of a recognised genetic syndrome or as a nonsyndromic isolated trait. Excluding third molars, the reported prevalence of hypodontia ranges from 1.6 to 6.9%, depending on the population studied. Most affected individuals lack only one or two teeth, with permanent second premolars and upper lateral incisors the most likely to be missing. Both environmental and genetic factors are involved in the aetiology of hypodontia, with the latter playing a more significant role. Hypodontia individuals often present a significant clinical challenge for orthodontists because, in a number of cases, the treatment time is prolonged and the treatment outcome may be compromised. Hence, the identification of genetic and environmental factors may be particularly useful in the early prediction of this condition and the development of prevention strategies and novel treatments in the future.