In this article, we examine the epidemiology and risk factors for the development of the most common mood disorders observed in the aftermath of TBI: depressive disorders and bipolar spectrum disorders. We describe the classification approach and diagnostic criteria proposed in the fifth edition of the Diagnostic and Statistical Manual for Mental Disorders. We also examine the differential diagnosis of post-TBI mood disorders and describe the mainstay of the evaluation process. Finally, we place a special emphasis on the analysis of the different therapeutic options and provide guidelines for the appropriate management of these conditions.