Image registration is finding increased clinical use both in aiding diagnosis and guiding therapy. There are numerous algorithms for registration, which all involve maximizing a measure of similarity between a transformed floating image and a fixed reference image. The choice of the similarity measure depends, to some extent, on the application. Methods based on the use of the joint intensity histogram have become popular because of their flexibility and robustness. A distinction is made between rigid-body and non-rigid transformations. The latter are needed for inter-subject registration or intra-subject registration in cases where the region of the body of interest is not considered rigid. Non-rigid transformation is normally achieved using a global model of the deformation but can also be defined by a set of locally rigid transformations, each constrained to a small block in the image. There is scope for further research on the incorporation of appropriate constraints, especially for the application of non-rigid transformations to nuclear medicine studies. Most of the initial practical concerns regarding image registration have been overcome and there is increasing availability of commercial software. There are several approaches to the validation of registration software, with validation of non-rigid algorithms being particularly difficult. Studies have demonstrated the accuracy on the order of half a pixel for both intra- and inter-modality registration (typically 2 to 3 mm). Although hardware-based registration has now become possible by using dual-modality instruments, software-based registration will continue to play an important role in nuclear medicine.