Determination of individual pharmacokinetics in patients undergoing radiopharmaceutical therapy is essential to define critical normal organ dosimetry. Review of a 20 year single institution experience demonstrates practical methodology for routinely characterising pharmacokinetics in each patient and calculating safe, effective therapeutic activities predicated upon prescribed radiation absorbed doses to the critical organs. In particular the results achieved in over 100 unselected consecutive clinic patients treated with (131)I-rituximab radioimmunotherapy for relapsed/refractory non-Hodgkins lymphoma have matched the ORR of 75% and CR 50% achieved in formal phase II clinical trial. The low level of myelotoxicity was attributed to prospective dosimetry in each patient and prescribed dose of 0.75 Gy to whole body. Radiopeptide therapy of progressive neuroendocrine tumours with (177)Lu-octreotate, illustrates application of practical dosimetry using retrospective quantitative imaging to define individual pharmacokinetics. Further challenges of multimodality combination therapy using radionuclide cocktails, chemotherapy and antivascular therapy, which will perturb pharmacokinetics, will require creative dosimetric methodology for continued safe, effective clinical practice of therapeutic nuclear oncology.