We analyzed toxicity and efficacy of second allogeneic hematopoietic stem cell transplantation (HSCT) or donor lymphocyte infusions (DLI) in 66 patients relapsing with acute myeloid leukemia (n = 15), acute lymphoblastic leukemia (n = 5), chronic myeloid leukemia (n = 14), non-Hodgkin's lymphoma (n = 14), myeloma (n = 8), myelodysplastic syndrome (n = 8), and metastatic renal cell carcinoma (n = 2). Forty-one patients were given second HSCT and 25 DLI. Sixteen patients (39%) are alive and disease-free after a second HSCT including 13 who had received nonmyeloablative conditioning. Thirteen patients (52%) are alive after DLI with mainly chronic myeloid leukemia patients in continuous complete remission. Relapse after HSCT is still a challenging situation and further studies to improve outcome of these patients are warranted.