This overview highlights the use of experimental models in selecting monoclonal antibodies and radiolabels with promise for clinical radioimmunotherapy, discusses some of the experimental therapeutic approaches being studies in these models, and reviews some of the limitations of animal models caused by the allometric and other differences between man and mouse. These differences in scale must be considered when attempting to extrapolate animal radioimmunotherapy study data to human trials of radioimmunotherapy. With appropriate recognition of their limitations, experimental models of radioimmunotherapy have proven valuable and will continue to play a critical role as the place to first study innovations in radioimmunotherapy, before extension of the most promising reagents and treatment concepts into clinical therapeutic trials.