The classification and genetic codification of human histocompatibility antigens (HLA), as well as the participation of these membrane structures in the stimulation mechanism of immune system and functional cell clones formation derived from T and B lymphocytes are reviewed in this work. In addition we present an up-date about the numerous association between HLA molecules expression and different human diseases described. The main mechanisms that have been proposed to explain the reasons for that associations are also presented; however we clarify that none of these can be consider as a proof of HLA participation in the etiopathogeny of those diseases. The HLA determination may help the physician to evaluate the risk of disease presentation and some of its complications as well as the prevention through the genetic advice.