Advances in sequencing technology and the resulting deluge of molecular sequence data have provided vast opportunities to study the evolution of gene and protein families together with the phylogenetic relations of the species harboring them. Each family of homologous sequences can provide hundreds or thousands of characters, that is, all homologous sites making up a sequence alignment, that are a potential source of valuable information for phylogenetic tree reconstruction. Moreover, molecular sequences have other advantages over, say, morphological characters. Among these, is a natural, unambiguous definition of “evolutionary distance”, which allows estimating the amount of evolutionary divergence of sequences, represented in phylograms. This precise definition of evolutionary distance stimulated the development over the last 35 years of evolutionary models that provide means to estimate evolutionary relations and to develop theories on how molecular sequences evolve, connecting phylogenetics to evolutionary biology.