The Mediterranean area has always played a significant role in human dispersal due to the large number of migratory events contributing to shape the cultural features and the genetic pool of its populations.This paper aims to review and diachronically describe the mitogenome variability in the Mediterranean population and the main demic diffusions that occurred in this area over time.Frequency distributions of the leading mitochondrial haplogroups have been geographically and chronologically evaluated. The variability of U5b and K lineages has been focussed to broaden the knowledge of their genetic histories.The mitochondrial genetic makeup of Palaeolithic hunter-gatherers is poorly defined within the extant Mediterranean populations, since only a few traces of their genetic contribution are still detectable. The Neolithic lineages are more represented, suggesting that the Neolithic revolution had a marked effect on the peopling of the Mediterranean area. The largest effect, however, was provided by historical migrations.Although the mitogenome variability has been widely used to try and clarify the evolution of the Mediterranean genetic makeup throughout almost 50 000 years, it is necessary to collect whole genome data on both extinct and extant populations from this area to fully reconstruct and interpret the impact of multiple migratory waves and their cultural and genetic consequences on the structure of the Mediterranean populations.