The perioperative pain management for craniotomies can be extremely challenging. This chapter presents a common clinical scenario and offers options for perioperative pain management. It presents a case study of a 52-year-old female American Society of Anesthesiologists class 3 patient presented for clipping of a cerebral aneurysm. The case described is a common example of the complexity frequently associated with neurosurgical patients. The combined regimen provided for analgesia and hemodynamic control, while allowing for an adequate neurologic examination. In addition, opioids were limited, thereby decreasing the risk of postoperative nausea and vomiting. Opioids are a key component of intraoperative and postoperative pain management for craniotomies. Morphine can cause histamine release, which can lead to venodilation and subsequent hypotension. A combination of intravenous analgesics and regional anesthesia can provide excellent pain relief and decrease the wide hemodynamic changes that can accompany anesthesia and surgery.