Various studies of economic and geographical relations in Russian regions often overemphasise the role of economy. However, the quality and quantity of human resources is one of the key factors behind distribution and development of production. Human resources are of even more importance in the Kaliningrad exclave. This paper aims to increase understanding of the role of human resources in the economic development of the Kaliningrad region. The study uses the cohort component method, scenario-based forecasting of the development and application of human resources, and econometric calculations of the comparative efficiency of human resources application across a range of economic activities. The author puts forward a number of recommendations for a better application of labour resources through sectoral restructurization of economy (which requires a higher value-added standard and has to be consistent with local natural, human, and innovation resources) and through improvement of the professional training system.