The Major Depressive Disorder is often episodic, meaning that while eventual recovery from an initial episode is likely, the risk of reoccurrence is also high. This chapter focuses on Diagnostic and Statistical Manual of Mental Disorders (DSM-5), which discusses the diagnostician to consider the possibility of Major Depressive Disorder in a bereaved person who displays intense sadness, poor concentration, insomnia, and guilt. Dr. Davidson noted that Barbara's feelings of emptiness and loss worsened with thoughts or reminders of her husband, but what seemed even more significant to him were the persistence of Barbara's depressed mood over almost a year and her lack of happiness or pleasure even when her mind was engaged in other activities. The chapter explores that a portion of Barbara's treatment consisted of taking a medication that selectively works on holding serotonin out in the synapse rather than allow it to be taken up by the nerve fiber.