We review the development of neurosurgery at the Medical University of South Carolina (MUSC) and the emergence of MUSC as a leading academic neurosurgical center in South Carolina. Historical records from the Waring Historical Library were studied, former and current faculty members were interviewed, and the personal records of Dr Phanor J Perot were examined. Dr Frederick E Kredel was the first to perform cerebral revascularization in stroke patients using omental flaps and the first to culture glioma cells in artificial media. The MUSC Neurosurgery residency program was established in 1964 by its first formally trained neurosurgeon, Julian Youmans, MD. The first graduate of the program, Dr Russell Travis, went on to become the President of the American Association of Neurological Surgeons. In 1968, the longest serving chairman, Dr Perot, joined the department and conducted significant research in spinal cord injury, receiving a continuous, 20-year award from the National Institute of Neurological Disorders and Stroke. A major change in the neurosurgery program occurred in 2004 when Dr Sunil Patel accepted the chairmanship. He integrated neurosurgery, neurology, and basic neuroscience departments into a comprehensive Department of Neurosciences to provide integrated clinical care. This department now ranks second in the country in National Institutes of Health research funding. Recently, the Center for Global Health and Global Neurosurgery was established with a vision of caring for patients beyond national borders. Neurosurgery at MUSC has been influenced by Drs Kredel and Perot and the current leadership is moving forward with a uniquely integrated department with novel areas such as global neurosurgery.