Unemployment is often taken as an indicator of the economic situation of a country, influenced by numerous macroeconomic, institutional and other variables, and denoting its complexity. Analysing unemployment solely on the basis of trends in unemployment rates is not entirely correct because the reduction of the unemployment rate may not indicate an improvement in the labour market situation. The ultimate goal of the unemployment rate reduction is essentially the improvement of the labour situation as the most important productive resource of the new economy. An efficient labour market strives to use labour as a productive factor to the satisfaction of the workforce and the economy in general. The doctoral dissertation deals with the study of unemployment determinants in the Central and South-eastern Europe countries for the period from 2000 to 2015. Common unemployment determinants of the countries of Central Europe, South-Eastern Europe and especially the Western Balkans as part of the countries of South-East Europe are studied through time series panel regression analysis. The countries of Central Europe represent developed countries, the countries of South-East Europe are less developed, and the countries of the Western Balkans are the least developed countries. The determinants of unemployment at the country level and for the period before and during the great global economic crisis are also studied to distinguish its impact on the efficiency of the observed labour markets. There are differences in the determinants of unemployment in the Central European and South-Eastern European countries and within each individual group considering the differences in the impact of macroeconomic and institutional factors on unemployment. Also, there are differences in the determinants of unemployment in Central and South-East Europe before and during the economic crisis that began in 2008.