Leukocyte adhesion deficiency II (LAD II) belongs to a group of human congenital diseases in which the interactions of leukocytes with the vascular endothelium are strongly impaired. LAD II is based on a defect in the synthesis of fucosylated glycostructures. This leads to an immunodeficiency owing to the absence of functional selectin ligands and to strong psychomotor defects, as a result of as-yet unknown reasons. In this review we focused on the current controversies, and open questions that have arisen from recent studies on the genetic defect, therapy and the basis of psychomotor defects in LAD II.