Delirium is a common diagnosis within the critically ill cancer population. It is characterized by acute and rapid fluctuations in mental status and consciousness. The diagnosis of delirium can be difficult and is often accomplished with the use of a validated delirium assessment tool. The prevalence of delirium varies widely with higher rates in patients who are elderly, have severe critical illness including cancer, or are known to have preexisting cognitive impairment and dementia. The pathophysiology of delirium is highly complex and may be related to changes in the brain as a result of neuroinflammation, endothelial dysfunction, aberrant cerebral perfusion patterns, and deficiency or abnormal activity of neurotransmitters. The prevention of delirium in the critically ill involves multiple components including choice of pain and sedating medications, early physical and occupational therapy, improving sleep, and daily awakening and breathing trials. There are no FDA-approved pharmacologic treatments available for delirium, though some of the antipsychotics and dexmedetomidine have shown promise in various studies. Delirium can be a challenging and deleterious diagnosis for critically ill cancer patients, but with proper recognition, as well as validated preventative and management strategies, the negative consequences associated with delirium can be decreased.