Targeted radionuclide therapy holds promise as a new treatment for cancer. Advances in imaging are making it possible for researchers to evaluate the spatial distribution of radioactivity in tumors and normal organs over time. Matched anatomical imaging, such as combined single-photon emission computed tomography/computed tomography and positron emission tomography/computed tomography, has also made it possible to obtain tissue density information in conjunction with the radioactivity distribution. Coupled with sophisticated iterative reconstruction algorithms, these advances have made it possible to perform highly patient-specific dosimetry that also incorporates radiobiological modeling. Such sophisticated dosimetry techniques are still in the research investigation phase. Given the attendant logistical and financial costs, a demonstrated improvement in patient care will be a prerequisite for the adoption of such highly-patient specific internal dosimetry methods.