This review summarizes the results of the long-term studies performed at the Institute of General Genetics, Russian Academy of Sciences, in the field of genetic demography of migration processes in Russia and its capital. The main population-genetic parameters of migration and their dynamics in Moscow over a hundred years are given. Sociodemographic and population-genetic implications of migration processes are considered. A model predicting the population gene pool dynamics under migration pressure for genes of different localization (autosomal, sex-linked, and mitochondrial), exemplified by predicting the allele frequency dynamics in the Moscow population of some gene markers, including genes accounting for monogenic pathology and genes associated with resistance to socially significant diseases, are presented. The paper discusses the selective character of migration processes, in particular, processes of emigration, with respect to some genetically significant ethnodemographic traits; the problem of adaptation of migrants; and adaptive strategies of consolidation of ethnoconfessional groups in the megalopolis (compact settlement over the urban territory and positive assortative mating with respect to demographic traits). It was shown that, owing to the intense influx of migrants and gene flows between ethnic groups, the population of the megalopolis is of mixed origin in terms of ethnic, anthropologic, and genetic aspects. The results of the study suggest the necessity to develop a specific strategy of genetic database formation for the population of megalopolises for the purposes of medical genetics and forensic medicine.