Iron deficiency in heart failure is a frequent condition and may be a prerequisite for the development of anemia but not necessarily the two conditions coexist. Iron deficiency in itself independently of the presence of anemia, determines a series of alterations of the cellular processes of our body related to the production of energy in the form of ATP, cell proliferation and DNA synthesis. The causes of iron deficiency are several and among the various, the inflammatory state present in chronic heart failure, combined with the absorption deficit seems to play a predominant role. This review aims to cover all the main aspects related to iron deficiency in patients with heart failure starting from aetiology up to the therapeutic implications. In particular, the different causes and the pathophysiological mechanisms that underlie the iron deficiency will be examined, describing what are the consequences on the alterations on the biochemical processes in terms of absorption, transport and use of iron by target cells with particular regard to muscle cells and Erythropoietic line. The meaning, the role and the importance in clinical practice of the different laboratory tests that dose the iron (Ferritin, Serum Iron, Transferrin and Transferrin saturation or TSAT) that allow to identify the presence of absolute or relative iron deficiency will also be underlined. Literature data related to the consequences of iron deficiency and to the alterations concerning its transport on the symptoms and functional capacity of patients with heart failure will be reported as well as their impact on prognosis. A second part of the paper will address the main aspects related to iron therapy. We will discuss the administration of iron per os with regard to the different drugs, to the processes of absorption and to the use of different pharmaceutical formulations with their associated side effects. The scientific evidences on parenteral formulations and in particular on the use of Fe-carboxymaltose will be reported. Finally, we will discuss the role of erythropoietin in the context of heart failure.