AbstractDisruptive mood dysregulation disorder (DMDD), a relatively new diagnosis in child and adolescent psychiatry that remains without medications approved for its indication, warrants a renewed consideration of the ethics surrounding the off-label use of medications. In the absence of empirical studies, clinicians must work with the best available information regarding treatment, such as case reports demonstrating the success of off-label interventions. Although subject to ethical limitations and the risk-benefit profile of each medication, increased use of this approach in the treatment of DMDD is warranted. A review of the literature was undertaken to identify studies for inclusion in this article. A case history of a 12-year-old girl with DMDD who was treated with amantadine with good response illustrates these ethical considerations within a clinical context. There are significant benefits of off-label uses of medications in the treatment of DMDD. The promising potential of amantadine as an agent for off-label use for pediatric populations with DMDD illustrates this approach. In the absence of approved medications for DMDD, further attempts to use off-label treatments for this disorder are warranted despite ethical constraints and varying risk-benefit profiles for each medication.