Radioimmunotherapy represents a significant advance over unlabeled immunotherapy for the treatment of patients with B-cell non-Hodgkin's lymphoma. The efficacy of radioimmunotherapeutic agents depends in large part on the basic biological effects associated with their components, monoclonal antibodies and radionuclides, separately and in combination. The radiobiological effects associated with yttrium 90-labeled ibritumomab tiuxetan (Zevalin; Biogen Idec Inc, Cambridge, MA) include the induction of apoptosis and cell-cycle redistribution (eg, arrest of cells in the G(2)/M phase of the cell cycle). Because of dose-rate effects, tumor cells may, in some cases, be more susceptible to the low-dose-rate radiation used in radioimmunotherapy than to the high-dose-rate radiation used in external beam radiotherapy. The efficacy of radioimmunotherapy may potentially be optimized through a variety of approaches, including the use of agents that increase the expression of certain tumor antigens (thus facilitating improved biodistribution of radiolabeled monoclonal antibodies) or that sensitize tumor cells to radiation.