Abstract: During radiotherapy, for a single organ, the anatomical and spatial heterogeneity to radiation response is usually not taken into consideration. With the development of imaging, radiation techniques and radiobiology, intensity-modulated radiotherapy may spare functional substructures in the organs. In this review, various critical functional structures were addressed and these functional substructures including the critical brain structure, neural nuclei and nerve fi ber tracts in the central nervous system, head and neck structures related to radiation-induced salivary and swallowing dysfunction, and functional substructures in lung and heart. During intensity-modulated radiotherapy, the dose-volume constraints could be set individually to minimize the radiation dose and(or) irradiated volume of various substructures without compromising the dose coverage to target volume.