Iron deficiency anemia (IDA) is estimated to affect over 1.2 billion people worldwide and is particularly common in children and reproductive-age women in low- and middle-income countries. Iron deficiency (ID) without anemia has an even higher prevalence. Absolute ID is caused by increased iron requirements, inadequate iron intake, impaired iron absorption, and chronic blood loss. ID triggers multiple adaptive physiological mechanisms, including modifications in cellular iron handling orchestrated by iron regulatory proteins, as well as alterations in systemic iron handling secondary to suppression of the iron regulatory hormone hepcidin. The laboratory diagnosis of ID is based on biochemical parameters and may be complicated during inflammatory conditions. ID is treated with oral or parenteral iron supplements, depending upon the severity of ID and its underlying cause(s). An improved understanding of systemic iron regulation has begun to inform oral iron dosing regimens and the selection of oral versus intravenous iron formulations for the management of ID.