We report a case series on the observed effects of low-dose ketamine infusions in 4 critically ill patients with varying complications related to prolonged critical illness. Doses of ketamine infusion ranged from 0.5 to 4 μg/kg/min. A low-dose ketamine infusion was used to reduce agitation in a patient requiring high doses of sedatives and analgesics. In a second patient, ketamine improved depression and anxiety symptoms. In a third patient, ketamine may have facilitated liberation from mechanical ventilation. In a fourth patient, ketamine was used for palliation to avoid lethargy. Ketamine may be considered to help decrease agitation, manage pain, facilitate opioid and benzodiazepine withdrawal, prevent respiratory depression, and potentially manage depression and anxiety in chronically critically ill patients.