OBJECTIVE: Iron deficiency and particularly iron deficiency anemia (IDA) can lead to negative health consequences. This review describes the importance of adherence and persistence (adhering to treatment for the recommended duration) with iron replacement therapy in the prevention of complications, particularly regarding its recommended dosing schedule. METHODS: Comprehensive literature searches were performed of Medline and the Cochrane library from 2000 to 2018. Keywords included iron deficiency or IDA, compliance or adherence, persistence, health beliefs, risk factor, complications, dosing cycles, oral iron replacement therapy and recommendations for duration, ferrous compounds, iron supplementation, dietary iron, and delayed-action/slow-release preparations. RESULTS: Identified articles focused on IDA as a risk factor (particularly for worsened comorbidities or surgical outcomes), guidelines, adherence and persistence, and differences between iron formulations. Current guidelines and expert opinion continue to support oral iron supplementation as first-line therapy. While it is recommended to take iron therapy for 2 months to normalize hemoglobin, then 2-3 months to build up iron stores, many patients face difficulties in adhering to and persisting with the full iron treatment regimen. Patient education and understanding, social support, simple dosing, perceived efficacy including reduced symptoms and tolerability were factors noted to promote medication adherence and persistence. Adherence to iron therapies appears to be facilitated by using ferrous sulfate due to its optimal absorption, and particularly extended-release forms due to their improved tolerability for iron deficiency. CONCLUSIONS: Proper adherence and persistence with iron supplementation may prevent or reduce the risk of complications of iron deficiency and IDA.