The field of structural biology has received a major thrust, thanks to the important advancements in cryo-electron microscopy coupled with the development of highly reliable computer-predicted structural models. Throughout evolution, the tertiary structure of proteins is more conserved than their primary structure. The superposition of protein tertiary structures has been a powerful tool in the identification of proteins with remote homology, whose evolutionary footprints are no longer detectable through their primary sequence alignment, and more recently in the reconstruction of evolutionary trees. These structure-based phylogenetic trees have been demonstrated to be quite useful in the study of deep evolutionary events and in the analysis of biological entities with extremely high mutation rates, such as RNA viruses. The construction of phylogenetic trees from tertiary structures starts by performing pairwise comparisons between a set of proteins, from which certain parameters, such as the number of spatially aligned residues and the average distance between their ɑ-carbons, are collected. These measurements are then used to calculate a structural distance metric, which can be used as input for the construction of an evolutionary tree.