The first bone marrow transplants (BMTs) in human patients were performed after conditioning with total body irradiation (TBI). TBI remains an important part of BMT protocols. The morbidity and mortality of BMT remains significant, but can be decreased by the introduction of optimized TBI regimens. This requires dosimetric control and a detailed analysis and description of the physics of the TBI procedure in every BMT center that utilizes TBI. Recommendations for such procedures are given. Radiobiological models are of help in developing less toxic TBI procedures, but can only be effective after dosimetric control has been obtained and if the influence of other variables on the outcome of BMT are taken into account. Fractionated TBI (fraction size over 3.0 Gy or higher) appears to be more effective and better tolerated than single fraction TBI. Lung shielding is possible during TBI. Smaller organs or organs that cannot be imaged easily are not recommended for shielding. Radiolabeled immunoglobulins are but low molecular weight bone seeking radioisotopes and are not expected to improve the therapeutic ratio of TBI. Other variables in BMT are more difficult to quantify and model than TBI (e.g. high-dose chemotherapy, graft-versus-host disease) and will be more difficult to optimize.