Vertebrates, often considered as the most sophisticatedly organized animals, have a number of unique morphological features that ensured their evolutionary stability and success. Many have argued that the genetic basis for these innovations was provided by the genome duplications occurred at the early stages of vertebrate evolution. One of the important results of genome duplication is the emergence of additional copies of regulatory genes. Having been removed from the constraining pressure of natural selection, these copies acquired an opportunity to modify their structure and functions, influencing the organism’s development and morphology. The consequence of ancient genomic duplications is, for example, that about 35% of human genes are represented by at least two homologous copies. The idea of genome duplications occurred at the early stages of vertebrate evolution was first proposed in 1970, but questions about the number, the scale (whole-genome or local) and the evolutionary timing of these duplications are still actively debated. In recent years (2018–2020), due to the rapid development of methods for processing of big data of high-throughput genome sequencing in different lineages of vertebrates and their closest relatives, cephalochordates and tunicates, a number of comparative studies aimed at identifying groups of syntheny in genomes of different evolutionary lines and reconstruction of ancestral vertebrate chromosomes were obtained. As a result, several models describing putative scenarios of genome duplications in vertebrate evolution have been proposed. In parallel, detailed laboratory studies focused on the expression and functional properties of different families of regulatory genes were performed for representatives of several vertebrate groups. In these studies, a plethora of new information on the molecular mechanisms of the embryonic development in hitherto poorly studied representatives of the evolutionarily ancient vertebrate linages (e.g. cyclostomes, cartilaginous fishes and sturgeons) have been collected. In this review, we consider modern concepts of the mechanisms and consequences of genomic duplications in the light of recent experimental data and currently proposed models of vertebrate genome evolution.