Heparin induced thrombocytopenia (HIT) remains the most severe adverse effect of heparin therapy. Recently, new information has been uncovered regarding the pathogenesis of this disorder. This review summarizes the clinical state, pathogenesis and diagnosis of HIT. It was stimulated by the recent recognition of heparin-platelet factor 4 (H. PF4) complexes as the major target antigen for heparin-dependent antibodies involved in this pathology. The formation of complexes between PF4 and heparin or other glycosaminoglycans, leading in some circumstances to the generation of antigenic structures reactive with HIT antibodies, is analysed. We also discuss how antibodies develop in heparin-exposed patients and why these antibodies can become pathogenic only in some patients, while their presence remains asymptomatic in others. This review also focuses on the mechanisms that could be involved in the development of thrombocytopenia and thrombosis. This new understanding of HIT pathogenesis has permitted the introduction of new tools for retrospective or prospective diagnosis, and may provide new strategies for the avoidance or treatment of HIT and its complications.