To explain the evolutionary mechanisms by which populations of organisms change over time, it is necessary to first understand the pathways by which genomes have changed over time. Understanding genome evolution requires comparing modern genomes with ancestral genomes, which thus necessitates the reconstruction of those ancestral genomes. This chapter describes automated approaches to infer the nature of ancestral genomes from modern sequenced genomes. Because several rounds of whole genome duplication have punctuated the evolution of animals with backbones, and current methods for ortholog calling do not adequately account for such events, we developed ways to infer the nature of ancestral chromosomes after genome duplication. We apply this method here to reconstruct the ancestors of a specific chromosome in the zebrafish Danio rerio.