Background: Deformable image registration (DIR) is increasingly used in the field of radiation therapy (RT) to account for anatomical deformations. The aims of this paper are to describe the main applications of DIR in RT and discuss current DIR evaluation methods. Methods: Articles on DIR published from January 2000 to October 2018 were extracted from PubMed and Science Direct. Our search was restricted to articles that report data obtained from humans, were written in English, and address DIR methods for RT. A total of 207 articles were selected from among 2506 identified in the search process. Results: At planning, DIR is used for organ delineation using atlas-based segmentation, deformationbased planning target volume definition, functional planning and magnetic resonance imaging-based dose calculation. In image-guided RT, DIR is used for contour propagation and dose calculation on per-treatment imaging. DIR is also used to determine the accumulated dose from fraction to fraction in external beam RT and brachytherapy, both for dose reporting and adaptive RT. In the case of reirradiation, DIR can be used to estimate the cumulated dose of the two irradiations. Finally, DIR can be used to predict toxicity in voxel-wise population analysis. However, the evaluation of DIR remains an open issue, especially when dealing with complex cases such as the disappearance of matter. To quantify DIR uncertainties, most evaluation methods are limited to geometry-based metrics. Software companies have now integrated DIR tools into treatment planning systems for clinical use, such as contour propagation and fraction dose accumulation. Conclusions: DIR is increasingly important in RT applications, from planning to toxicity prediction. DIR is routinely used to reduce the workload of contour propagation. However, its use for complex dosimetric applications must be carefully evaluated by combining quantitative and qualitative analyses.