Allogeneic stem cell transplantation (allo-SCT) for haematological malignancies became a safer approach in recent years, for example, owing to improved supportive strategies. However, despite the efficacy of the procedure, morbidity and mortality mainly caused by infections and organ toxicity remain serious problems. Due to the variety of conditioning regimens being applied before allo-SCT, one important aspect is represented by the toxicity profiles of the specific compounds, which are being applied for the reduction of the leukaemia cell load and for immunosuppression. This is being illustrated by the hepatotoxic profile of busulfan with its high rate of veno-occlusive disease. However, recent advances in our understanding of drug metabolism, progress in the measurement of drug concentration, and the invention of some new drugs and therapeutic approaches in the conditioning period are promising steps in achieving more safety for patients undergoing allo-SCT. Reduced-intensity conditioning concepts allow the inclusion of heavily pretreated patients or patients with severe co-morbidities in transplantation concepts. New prophylactic regimens, including poly- or monoclonal antibodies, result in reduced rates of graft-versus-host disease, and some 'new' drugs such as treosulfan or clofarabine widen the range of available conditioning regimens for specific situations.