Hemochromatosis is a common genetic disorder in which iron may progressively accumulate in the liver, heart, and other organs. The primary goal of therapy is iron depletion to normalize body iron stores and to prevent or decrease organ dysfunction. The primary therapy to normalize iron stores is phlebotomy. In this opinion article, we discuss the indications for and monitoring of phlebotomy therapy to achieve iron depletion, maintenance therapy, dietary and pharmacologic maneuvers that could reduce iron absorption, and the role of voluntary blood donation.