Iron overload disorders are conditions that can lead to increased body iron stores and end-organ damage in affected organs. Increased iron deposition most commonly occurs in the liver, heart, endocrine system, joints, and pancreas. Iron overload disorders may be caused by genetic or acquired causes (transfusion, dyserythropoiesis, and chronic liver disease). The HFE gene C282Y homozygous mutation is the most common cause of hereditary hemochromatosis (HH). Other genes implicated in HH include TFR2, HAMP, HJV, and SLC40A1. In the past 2 decades, there have been major advances in the understanding of genetic iron overload disorders. Furthermore, new novel techniques to measure iron content in organs noninvasively, as well as new therapeutic options for the treatment of HH, are currently under development. This article focuses on the latest concepts in understanding, diagnosing, and managing genetic iron overload disorders, particularly HH.