After the introduction of cyclophosphamide and total body irradiation in the 1970s, a variety of conditioning regimens has been developed. However, none has proven to be superior. Fractionation of the irradiation results in less toxic side-effects, but the total dose has to be increased to obtain similar immunosuppressive effects. Data from randomized trials indicate that among patients with myeloid leukaemia, busulfan in combination with cyclophosphamide results in similar outcome, while a regimen containing total body irradiation is probably still the best for patients with acute lymphoblastic leukaemia. Busulfan treatment can be optimized by targeted steady-state concentration or with the use of intravenous preparations. Intensified regimens decrease the relapse incidence, but because of a higher mortality from transplant-related causes survival is unchanged. Reduced-intensity conditioning can reduce transplant-related mortality and offer otherwise ineligible patients a potentially curative treatment. Long-term results are unknown.