The paper presents the analysis of epidemic activity of natural plague foci around the world, including in CIS and the Russian Federation, over the period of 2000–2018. It was established that in 2010–2018, epidemic manifestations took place in natural plague foci where the main carriers are synanthropic (black, multinippled rats) and commercial (marmots, souslik, ground squirrels) species of rodents. Retaining of low epizootic activity of lowland natural plague foci in the territory of the Russian Federation is observed. In 2018, plague epizooties were detected in the territory of the Gorno-Altai high-mountain and Tuva mountain natural foci, the total coverage area being 2641 km2. 13 strains of the main subspecies and 6 strains of Altaic subspecies of plague microbe were isolated. Demonstrated were the prospects of GIS-technology usage for the enhancement of epidemiological surveillance over plague in Russia. Epizootiological forecast for persisting challenging epidemiological situation in Kosh-Agach district of the Republic of Altai and Mongun-Taiginsky, Ovyursky and Tes-Khemsky Kozhuuns of the Republic of Tuva was substantiated. Recorded was high probability of retention of strained epizootic and epidemiological situation in the south and central parts of the desert zone in the Republic of Kazakhstan, high-mountain areas of the Republic of Kyrgyzstan. Also conservation of epidemic risks for the territories of the countries in Africa (Republic of Madagascar), South (Peru, Bolivia), and North (USA) America, China, and Mongolia was noted.