Improvement of immune reconstitution after haematopoietic stem cell transplantation (HSCT) is a key issue determining the clinical outcome of this widely used therapeutic approach. To this end, new strategies have been prompted by recent discoveries in immunology. In the setting of human leukocyte antigen (HLA) geno(pheno)identical HSCT, better prevention and treatment of acute and chronic graft-versus-host disease (GvHD) could significantly attenuate the thymic epithelium damage responsible for delayed and incomplete T-cell reconstitution. In a haploidentical setting, methods that would significantly accelerate neothymopoiesis in the months following injection of highly purified CD34+ cells are warranted. If these objectives could be achieved, the haploidentical procedure would become more readily available to patients affected by acquired or inherited disorders of the haematopoietic system.