Mugilidae (Teleostei) include over 70 species worldwide, and approximately 25% of them have been cytogenetically analyzed. Although a review of Mugilidae genetics was recently published, new data have provided a different perspective on the cytotaxonomic relationships of this group and generated a revision of the chromosomal evolution of their family. Most mugilid species possess the conservative 48-uniarmed chromosome karyotype, with some differences hinging on the presence or absence of short arms on a sole subtelocentric chromosome pair, thus allowing the identification of two distinct cytotypes, namely A and B, respectively. Differences in constitutive heterochromatin and in the location of genes 18S and 5S rRNA can be found within and between these two cytotypes. A recent analysis of the karyotype of Agonostomus monticola, the family’s most basal species, ascertained that it possesses the B cytotype; and offers the opportunity to both reconsider relations between the two cytotypes and infer the direction of chromosomal changes during the evolution of the group, suggesting that cytotype B could be closer to the ancestral karyotype. Mugil curema is an exception to this scenario, having two different cytotypes (C1 and C2) in terms of number of chromosomes, NOR location, and heterochromatin distribution, though both are mainly or exclusively constituted by biarmed chromosomes. However, neither of the cytotypes (A or B) currently described in the family can be identified as being closer to the ancestral karyotype that underwent the Robertsonian fusion observed in the two C cytotypes; nor is it possible to infer a direct cytotaxonomic relationship between cytotypes C1 and C2. The cytogenetic features of the family entail a great opportunity to carry out cytotaxonomic and phylogenetic studies as well as structural, evolutionary, and functional analyses of the genome, i.e., a cytogenomic approach. This entails the isolation and cloning of additional satellite DNA families and the production of specific painting probes to allow for whole chromosome painting, whose distribution in the karyotypes of different mugilid species will allow the investigation of inter-specific homologies and structural changes leading to mullet chromosomal complement divergence.