Response and toxicity prediction is essential to rational implementation of cancer therapy. The biologic effects of radionuclide therapy are mediated via a well-defined physical quantity, the absorbed dose, which is defined as the energy absorbed per unit mass of tissue. The concepts, basic definitions, and different approaches to the clinical implementation of absorbed dose estimation are reviewed in this article. Ongoing efforts to improve the accuracy of dosimetry calculations are discussed, as well as studies examining the relationship between absorbed dose and response. Particular attention is placed on the marrow and kidney as dose-limiting organs. Finally, the potential role of radiobiologic modeling in helping to account for differences in dose rate and spatial distribution are reviewed. A treatment planning approach to radionuclide therapy will eventually require incorporation of biologic and radiobiologic considerations. Until such methods are developed and validated, absorbed dose remains an important variable--but still one of several--likely to predict response in an individual patient.