The aim of this literature review was to examine the evidence for psychotherapeutic and pharmacological treatments in subjects with severely dysregulated mood and to identify potential areas for improvements in research designs. A literature search was conducted using several databases for published (PubMed, PsycINFO) and ongoing (clinical trial registries) studies conducted in youths who met NIMH’s criteria for Severe Mood Dysregulation (SMD) or the DSM-5 diagnosis of Disruptive Mood Dysregulation Disorder (DMDD). Eight completed studies were identified: three randomized trials, four open pilot studies and one case report. Seven ongoing studies were found in trial registries. The available evidence suggests potential efficacy of psychotherapies which have previously been developed for internalizing and externalizing disorders. The two main pharmacological strategies tested are, first, a monotherapy of psychostimulant or atypical antipsychotic such as risperidone, already used in the treatment of severe irritability in youths with developmental disorders; and second, the use of a serotonergic antidepressant as an add-on therapy in youths treated with psychostimulant. Ongoing studies will further clarify the effectiveness of psychotherapeutic interventions for DMDD individuals and whether they should be given alone or in conjunction with other treatments. The short duration of the trials for a chronic disorder, the low number of studies, the lack of placebo or active comparator arm, and restrictive inclusion criteria in most of the controlled trials dramatically limit the interpretation of the results. Finally, future research should be conducted across multiple sites, with standardized procedures to measure DMDD symptoms reduction, and include a run-in period to limit placebo effect.