Iron-deficiency anemia resistant to iron administration is a common clinical problem. This paper analyzes the causes of primary failure of iron therapy. From a practical point of view, the main recommendation is that a physician should not be satisfied with simplicistic explanations for <<refractoriness>>. In fact, failure to respond to treatment is always the result of a diagnostic or therapeutic error which must be corrected in order to achieve the natural result of all substitution therapies: replenishment.