The article investigates the evolution of the Russian-Uzbekistani relations in the last years of the presidency of Islam Karimov (2012–2016). Based on a wide range of official sources and periodicals, it identifies the main trends, achievements and issues of bilateral cooperation in the political, trade, economic and humanitarian spheres. It determines the factors that influenced the interaction between Moscow and Tashkent, and pays a particular attention to the role of the presidents of the two states in the development and strength- ening of their cooperation. The author concludes that throughout the period under review the Rus- sian-Uzbekistani relations faced serious challenges. They were remarkably conflicting, unpredictable, inconsistent, and quite turbulent, what provoked the discussions about the correspondence of their real political condition to their high legal status (in 2004, Russia and Uzbekistan became strategic part- ners, and in 2005, allied states). Nevertheless, the two countries overcame most of their differences and took a course towards the further expansion and deep- ening, as well as modernization of their relations. As a result, at present Uzbeki- stan remains one of the most important Russia’s partners not only in Central Asia, but throughout the post-Soviet space, as well as within the framework of the leading international organizations.