The selected case study aimed to evaluate the role of phenobarbital as a drug of choice in end-of-life (EOL) settings. Phenobarbital is efficacious in management of EOL seizures and agitation, can be easily administered via different modes, and utilized in various palliative care (PC) settings. Mrs. X., 90-year-old female with a history of glioblastoma multiforme, was a resident of long-term care, residing in a PC unit. She presented with illness progression which resulted in an increased frequency of generalized tonic-clonic seizures which were managed initially with phenytoin. Due to the advanced stage of the illness and significant decline in the patient’s cognitive and physical status, oral route and intravenous access were lost, and phenytoin became not an option for seizure control. She was then rotated to subcutaneous phenobarbital, as a result, starting at 30 mg once a day. The dose needed to be titrated up in 15 mg increments to achieve adequate seizure control, and she stabilized on 60 mg of subcutaneous phenobarbital after 2 days. No serious adverse skin reactions were noted with the use of phenobarbital, and it did not abruptly end a patient’s life when used at appropriate doses. The sedative properties of phenobarbital had benefited Mrs. X and allowed her to be comfortable approaching EOL with glioblastoma multiforme.