Similar to other genera and species of bacteria, whole genomic sequencing has revolutionized how we think about and address questions of basic Vibrio biology. In this review we examined 36 completely sequenced and annotated members of the Vibrionaceae family, encompassing 12 different species of the genera Vibrio, Aliivibrio, and Photobacterium. We reconstructed the phylogenetic relationships among representatives of this group of bacteria by using three housekeeping genes and 16S rRNA sequences. With an evolutionary framework in place, we describe the occurrence and distribution of primary and alternative sigma factors, global regulators present in all bacteria. Among Vibrio we show that the number and function of many of these sigma factors differs from species to species. We also describe the role of the Vibrio-specific regulator ToxRS in fitness and survival. Examination of the biochemical capabilities was and still is the foundation of classifying and identifying new Vibrio species. Using comparative genomics, we examine the distribution of carbon utilization patterns among Vibrio species as a possible marker for understanding bacteria-host interactions. Finally, we discuss the significant role that horizontal gene transfer, specifically, the distribution and structure of integrons, has played in Vibrio evolution.