Global science expansion and the 'skills premium' in labor markets have been extensively discussed in the literature on the global knowledge economy, yet the focus on, broadly-speaking, knowledge-related personnel as a key factor is surprisingly absent. This article draws on UIS and OECD data on research and development (R&D) personnel for the period 1980 to 2015 for up to N = 82 countries to gauge cross-national trends and to test a wide range of educational, economic, political and institutional determinants of general expansion as well as expansion by specific sectors (i.e. higher education vs corporate R&D) and country groups (OECD vs non-OECD). Findings show that, worldwide, the number of personnel involved in the creation of novel and original knowledge has risen dramatically in the past three decades, across sectors, with only a few countries reporting decrease. Educational (public governance, tertiary enrolment and professionalization) and economic predictors (R&D expenditures and gross national income) show strong effects. Expansion is also strongest in those countries embedded in global institutional networks, yet regardless of a democratic polity. I discuss the emergence of 'knowledge work' as a mass-scale and worldwide phenomenon and map out consequences for the analysis of such a profound transformation, which involves both an educated workforce and the strong role of the state.