Dangerous, sustained elevation in intracranial pressure (ICP) is a risk for any patient following severe brain injury. Intracranial pressure elevations that do not respond to initial management are considered refractory to treatment, or rICP. Patients are at significant risk of secondary brain injury and permanent loss of function resulting from rICP. Both nonpharmacologic and pharmacologic interventions are utilized to intervene when a patient experiences either elevation in ICP or rICP. In part 1 of this 2-part series, pharmacologic interventions are discussed. Opioids, sedatives, osmotic diuretics, hypertonic saline solutions, and barbiturates are drug classes that may be used in an attempt to normalize ICP and prevent secondary injury. Nursing care of these patients includes collaboration with an interprofessional team and is directed toward patient and family comfort. The utilization of an evidence-based guideline for the management of rICP is strongly encouraged to improve patient outcomes.