The recent development of image analysis and visualization tools allowing explicit 3D depiction of both normal anatomy and pathology provides a powerful means to obtain morphological descriptions and characterizations. Shape analysis offers the possibility of improved sensitivity and specificity for detection and characterization of structural differences and is becoming an important tool for the analysis of medical images. It provides information about anatomical structures and disease that is not always available from a volumetric analysis. In this chapter we present our own shape analysis work directed to the study of anatomy and disease as seen on medical images. Section 2 presents a new comprehensive method to establish correspondences between morphologically different 3D objects. The correspondence mapping itself is performed in a geometry-and orientation-independent parameter space in order to establish a continuous mapping between objects. Section 3 presents a method to compute 3D skeletons robustly and show how they can be used to perform statistical analyses describing the shape changes of the human hippocampus. Section 4 presents a method to approximate individual MS lesions’ 3D geometry using spherical harmonics and its application for analyzing their changes over time by quantitatively characterizing the lesion’s shape and depicting patterns of shape evolution.