The main alternatives to non-rigid registration are rigid and affine equivalents, but these are rather impractical. In most real-world applications such as registration of brain-slice images, there is a very slim chance of getting satisfactory alignment of structures while preserving some continuity unless non-rigid transformations are applied. One may argue that affine registration should suffice, but what if parts of the brain expand beyond proportion? It therefore appears as if, from a registration point-of-view, no obvious alternatives are yet known. The ones mentioned above give the best performance yet and comparison with the closely-related active appearance models suggests that flexible deformation is mandatory, especially for biomedical data.