Objectives: To determine the relationship between the need for orthodontic treatment and OHRQoL in children and adolescents, and to identify potential modifying factors of this relationship. Methods: Systematic review, starting with searches of PubMed, Scopus, and EBSCO Discovery Service. Observational studies which examined the relationship between the need for orthodontic treatment and OHRQoL, in children and adolescents, were considered eligible. Results: Eighteen studies were included, of which, one was a prospective cohort study and 17 were cross-sectional. Twelve of 18 studies reported a relationship between the need for orthodontic treatment and OHRQoL, while the remainder failed to demonstrate a clear relationship. Gender and self-esteem were found to modify this relationship. Conclusions: Need for orthodontic treatment is associated with OHRQoL in children and adolescents. Gender and self-esteem are potential effect modifiers of this relationship. Keywords: Adolescent, Quality of life, Child, Oral-health related quality of life, Orthodontic treatment need, Index for orthodontic treatment need