A general-purpose deformable registration algorithm referred to as ”DRAMMS” is presented in this paper. DRAMMS adds to the literature of registration methods that bridge between the traditional voxel-wise methods and landmark/feature-based methods. In particular, DRAMMS extracts Gabor attributes at each voxel and selects the optimal components, so that they form a highly distinctive morphological signature reflecting the anatomical context around each voxel in a multi-scale and multi-resolution fashion. Compared with intensity or mutual-information based methods, the high-dimensional optimal Gabor attributes render different anatomical regions relatively distinctively identifiable and therefore help establish more accurate and reliable correspondence. Moreover, the optimal Gabor attribute vector is constructed in a way that generalizes well, i.e., it can be applied to different registration tasks, regardless of the image contents under registration. A second characteristic of DRAMMS is that it is based on a cost function that weights different voxel pairs according to a metric referred to as ”mutual-saliency”, which reflects the uniqueness (reliability) of anatomical correspondences implied by the tentative transformation. As a result, image voxels do not contribute equally to the optimization process, as in most voxel-wise methods, or in a binary selection fashion, as in most landmark/feature-based methods. Instead, they contribute according to a continuously-valued mutual-saliency map, which is dynamically updated during the algorithm’s evolution. The general applicability and accuracy of DRAMMS are demonstrated by experiments in simulated images, inter-subject images, single-/multi-modality images, and longitudinal images, from human and mouse brains, breast, heart, and prostate.