Emotions and mood play a central role both in the outcome and the management of neurologic illness. The importance is magnified when faced with differentiating between a primary emotional etiology for presenting complaints and neurocognitive symptoms and the possibility of emotional symptoms being the result of a neurologic injury, or a process of dysfunction as a result of an attempt to adjust to changes produced from neurologic injury or neurodegenerative process. Differentiating among these three possibilities is not easy and depends as much on eliciting a detailed psychiatric history as it does on knowledge of the possible emotional sequelae of neurologic injury and anatomical correlates of emotional functioning. This chapter outlines the currently used multi-axial system of the Diagnostic and Statistical Manual of Mental Disorders, 5th edition, Text Revised (DSM-5-TR). This manual represents the currently accepted diagnostic criteria for mental disorders as outlined by the American Psychiatric Association and the American Psychological Association. While there is no shortage of controversy regarding the criteria for diagnosing mental illness, this system represents the best effort thus far to provide behavioral and objective criteria to a nosologically difficult area of medicine. The interested reader is referred to the DSM-5-TR referenced at the end of this chapter for a more detailed description of specific disorders.