Evidence in the recent literature has highlighted the importance of central corneal thickness (CCT) in relation to several ocular and non-ocular conditions. Most notably, thinner CCT has been identified as a risk factor for open-angle glaucoma. Despite having an extensive knowledge of the structure and function of the cornea, little is known about the pathways that determine CCT. There are data to suggest however that CCT has a strong genetic component. Heritability studies conducted in twins and family pedigrees indicate that CCT is one of the most highly heritable human traits, whereas data from a diverse range of ethnic groups show clear ethnic-related differences in CCT. Extreme CCT measurements have also been associated with rare genetic diseases. Although there is strong evidence supporting a genetic component to normal CCT variation, to date, no genes have been identified. This review investigates the current literature surrounding this topic and explores the significance of understanding the genetics of CCT and how this might benefit the field of open-angle glaucoma treatment and research.