Many challenges accompany new paraphyletic strategies for genome sequencing, where dense sets of closely related species and their strains are analyzed as a group. The data volumes are considerable, and quality of the data can also be less that what these labs have come to expect from genomes produced by traditional sequencing centers. But the principal problem is comparative annotation, which should exploit the comparative nature of the project, and use the comparison between the related species to improve the annotation process. Drawing on a number of large-scale comparative genomics projects we have developed over the past twelve years, we will illustrate these challenges, and extrapolate the needs of collaborative, robust, comparative methods for this kind of multi-genome project.