Orthorexia nervosa (ON) is defined as an exaggerated, obsessive, pathological fixation on healthy food, healthy eating, or health-conscious eating behaviors. In the literature, there is an ongoing debate over whether ON should be considered simply a lifestyle phenomenon or a psychiatric disorder. In this vein, ON seems to share psychopathological characteristics with both eating disorders (EDs) and obsessive-compulsive disorder (OCD). However, there are insufficient data to reconcile the debate. The present study aimed at consolidating evidence on the clinical significance of ON and its relationship with EDs and OCD. A selective review of the literature published between January 2015 and March 2022 was conducted, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Ten studies were included. Some of these studies suggested that ON might follow a full-syndrome DSM-5 ED. Other studies proposed that ON and DSM-5 EDs may co-occur. Finally, only two studies suggested a relationship between ON and OCD. To date, the clinical significance of ON and its relationship with EDs and other DSM-5 psychiatric disorders (e.g., OCD) appears complicated and unclear. Future longitudinal research on the possible clinical course of ON is needed.