What is trepanation? Trepanation is one of the world's oldest, surgical procedures. It is possibly the oldest. Trepanation is the practice of drilling a hole in the skull as a physical, mental, and/or spiritual treatment. It was practiced by many of the most ancient cultures, ranging from ancient Egypt to Meso-American cultures. Some of the information gathered from ancient cultures indicates they believed that trepanning could cure a number of things, including mental disorders. Trepanning was also performed on infants*.