The choice of dose and fractionation for total body irradiation is made difficult by the large number of considerations to be taken into account. The outcome of bone marrow transplantation after total body irradiation can be understood in terms of tumour cell killing, engraftment, and normal tissue damage, each of these endpoints being influenced by irradiation-, disease-, transplant-, and patient-related factors. Interpretation of clinical data is further hampered by the overwhelming influence of logistic constraints, the small numbers of randomised studies, and the concomitant variations in total dose and fraction size or dose rate. So far, three cautious conclusions can be drawn in order to tentatively adapt the total body irradiation schedule to clinically-relevant situations. Firstly, the organs at risk for normal tissue damage (lung, liver, lens, kidney) are protected by delivering small doses per fraction at low dose rate. This suggests that, when toxicity is at stake (e.g., in children), fractionated irradiation should be preferred, provided that interfraction intervals are long enough. Secondly, fractionated irradiation should be avoided in case of T-cell depleted transplant, given the high risk of graft rejection in this setting. An alternative would be to increase total (or fractional) dose of fractionated total body irradiation, but this approach is likely to induce more normal tissue toxicity. Thirdly, clinical data have shown higher relapse rates in chronic myeloid leukaemia after fractionated or low dose rate total body irradiation, suggesting that fractionated irradiation should not be recommended, unless total (or fractional) dose is increased. Total body irradiation-containing regimens, primarily cyclophosphamide/total body irradiation, are either equivalent to or better than the chemotherapy-only regimens, primarily busulfan/cyclophosphamide. Busulfan/cyclophosphamide certainly represents a reasonable alternative, especially in patients who may not be eligible for total body irradiation because of prior irradiation to critical organs.