The transplantation of megadoses of haploidentical hematopoietic stem cells is for a number of children with malignant or nonmalignant diseases the only curative approach. In order to prevent severe GvHD, the removal of T lymphocytes from the stem cell graft either by positive selection of CD34+ stem cells or by negative depletion of CD3+ T lymphocytes is necessary. We present the results obtained so far by CD34+ positive selection and discuss new techniques of graft engineering which might hopefully further improve the outcome of haploidentical stem cell transplantation.