This purpose of this article is to promote comprehensive assessment, differential evaluation and provision of care which optimizes benefit while minimizing burden. Delirium is a debilitating neuropsychiatric complication that is highly prevalent in palliative care. It is multifactorial and may be related to infection, disease progression, metabolic state or medication toxicity. There are three proposed sub-types of delirium with the hypoactive/ hypoalert variant being most often underdiagnosed and undertreated. The inadequate management of all types of delirium is associated with increased personal and family distress, lengthier hospital stays, and escalating healthcare costs. This article reviews the assessment, diagnosis and treatment for delirium in general and hepatic encephalopathy in particular. A number of valid and reliable tools are discussed, as they assist in screening, symptom appraisal, diagnosis, and treatment planning. It is recognized that nurses are particularly well positioned to make bedside observations, to document changes over time, and to educate and support patients and their families. Searching for the etiology of delirium, developing individualized plans of care consistent with patient goals, and endorsing the benefit of consultation/referral are discussed as key roles for palliative care providers from all disciplines. New and novel therapies in the management of hepatic encephalopathy are discussed, as they expand treatment options for patients at all points along the trajectory of liver disease.