Hepcidin is primarily secreted by the liver and functions as an endocrine hormone. However, a growing number of studies show that hepcidin can also be produced locally by other cells and organs, where it acts in an autocrine/paracrine manner to mediate important iron-dependent pathways. These pathways can operate under normal homeostatic conditions or become relevant in pathophysiological conditions (inflammation, infection, cancer, liver disease, myocardial infarction, etc.). This chapter will delve into the local roles of hepcidin, highlighting its unconventional functions in barrier maintenance, host defense, growth, tissue housekeeping, and injury repair.