Phlebotomy is an ancient medical procedure that has been performed for thousands of years. In the 20th century, evidence supporting the use of therapeutic phlebotomy (TP) in conditions such as including hereditary hemochromatosis, polycythemia vera, and secondary iron overload became available. Despite the widespread use, TP is sometimes viewed as an orphan procedure because there is lack of standardization in how, where, and by whom the procedure is performed. This session will review complications of iron overload, indications for TP, and complications/adverse events associated with TP. Potential billing challenges will be identified and addressed. Pediatric considerations will be explored, including necessary vascular access, and relative rates of iron removal in growing patients. Finally, a blood center’s perspective on optimizing their adult TP program will be explored.