Delirium remains the most common and distressing neuropsychiatric complication in patients with advanced cancer. Delirium causes significant distress to patients and their families, and continues to be underdiagnosed and undertreated. The most frequent, consistent, and, at the same time, reversible etiology is drug-induced delirium resulting from opioids and other psychoactive medications. The objective of this narrative review is to outline the causes of delirium in advanced cancer, especially drug-induced delirium, and the diagnosis and management of opioid-induced neurotoxicity. The early symptoms and signs of delirium and the use of delirium-specific assessment tools for routine delirium screening and monitoring in clinical practice are summarized. Finally, management options are reviewed, including pharmacological symptomatic management and also the provision of counseling support to both patients and their families to minimize distress.