Hepcidin, the master regulator of systemic iron homeostasis, modulates the absorption of dietary iron as well as its release from stores by blocking and inducing the degradation of ferroportin, the only known cellular iron exporter. Thus, the interaction between hepcidin and ferroportin negatively regulates iron transport into plasma and reduces systemic iron availability. Several genetic and acquired iron-related disorders are characterized by dysregulated hepcidin expression. While hereditary hemochromatosis and β-thalassemia exhibit hepcidin suppression, causing iron overload, iron-refractory iron-deficiency anemia and anemia of chronic diseases show hepcidin induction, promoting iron deficiency. In the last decade, experimental evidence demonstrated that targeting the hepcidin-ferroportin axis and restoring normal hepcidin levels offer potential therapeutic benefits to patients with iron-related disorders. Due to these reasons, the development of hepcidin therapeutics has been exponentially growing in recent years, with the aim to design hepcidin modulators that either mimic or inhibit hepcidin action, leading to reduced or increased iron availability, respectively. This chapter summarizes the current landscape of hepcidin therapeutics that reached clinical development and the pathologies that could benefit from these pharmacological approaches. Moreover, it provides novel experimental insights into new potential therapies combining hepcidin modulators with existing or novel approaches such as luspatercept or TfR2 targeting as a way to achieve further improvement of anemia in pathologic conditions.