The prescribed total radiation dose should be administered within a specific time. In daily clinical practice, however, unplanned treatment interruptions resulting in prolongation of the overall treatment time are predictable. The present review evaluated the existing published data regarding the affect of the prolongation of the overall treatment time on the tumor control rate and outcome of patients with head-and-neck, lung, and uterine cervical cancer and other treatment sites. In most studies, including the planned interruption (split-course) schedules, as well as the retrospective studies analyzing the role of overall treatment time, a detrimental effect from the treatment break on the outcome was evident. This is suggestive of the deleterious effect of accelerated repopulation of tumor clonogens. In particular for the cancers of the head and neck for which the evidence is the strongest for such a consequence, even a I-day interruption resulted in a decrease in the local control rate by 1.4%. Although the increased number of gaps was associated with a negative outcome, the data are contradictory concerning the effect of the number of gaps. The main recommendation is to exert all efforts to retain the planned irradiation schedule; however, existing data have shown that interruptions that effect the programmed timecourse for irradiation need to be compensated for. This is to ensure biologic equivalence in treatment efficacy compared with uninterrupted regimens with respect to cancer site and stage. Practical methods for compensation using radiobiologic modeling and their limitations are also discussed. (c) 2007 Elsevier Inc.