Since the World Health Organization broadened its definition of health, beyond biological boundaries, to include physical, emotional, and social wellbeing. Oral health-related quality of life (OHRQoL) became common outcome measure in clinical trials and epidemiological studies in Dentistry and Medicine. It is not surprising, therefore, to see quality of life as one of the programs of the Saudi 2030 vision. That said, it can be difficult to interpret the findings of OHRQoL research if the measures used were not appropriately adapted and validated in the population being studied. In this review article, the concept of cross-cultural adaptation of OHRQoL and its use in the Saudi context, as applied to orthodontic research, was discussed. An electronic search in PubMed and MEDLINE databases was conducted. A second search was conducted to locate methodological papers discussing cross-cultural adaptation and translations. Appraisal of relevant research was conducted to provide a better understanding of the process of adapting OHRQoL measures to assess the impact of malocclusion and dentofacial abnormalities on quality of life. This review pointed out important methodological concerns that warrant considerations during the translation and adaptation of OHRQoL measures.