OBJECTIVE: While dysfunction of serotonin and dopamine neurotransmitters has been studied in depth, in regard to the etiology of mental illness, the neurotransmitter glutamate and its dysfunction is now being explored as contributing to neurodegenerative psychiatric diseases, schizophrenia, autism, depression, and Alzheimer’s disease. This article explains its synthesis, neurotransmission, and metabolism within the brain and subsequent dysfunction that is responsible for neurocognitive loss associated with several psychiatric disorders. METHOD: The case study will report on the screening for pseudobulbar affective (PBA) disorder in a 29-year-old male with bipolar disorder, autism spectrum disorder, and intellectual developmental disability who was experiencing extreme, uncontrolled emotional outbursts requiring continuous family isolation (pre-COVID-19) for safety. With the positive screen for PBA, the patient was subsequently treated with a glutamatergic drug, dextromethorphan/quinidine. RESULTS: The patient’s unexpected response to this treatment including the acquisition of language, increased cognition, and improved executive functioning is presented. At 2 years post the initiation of treatment, his PBA screening score is reduced, uncontrolled outbursts and aggression have subsided, and the family can spend time outside of their home. CONCLUSIONS: Neurodegeneration and its impact is being researched and treated with medications affecting glutamate. The addition of a glutamatergic medication to this young man’s medication regimen has improved both his and his family’s quality of life. The psychiatric diagnoses, medications, and treatments associated with glutamate are explained in depth. The importance of nurses’ understanding of glutamate, its synthesis, transmission, and dysfunction causing excitotoxicity and brain cell death and its impact on patients’ behavior and safety is explained.