Although Principal Investigators are key actors in scientific fields, there is little focus on what they actually do in shaping new scientific directions. This paper studies PIs practices to better understand their roles. Our central contribution is to identify the different ways in which PIs engage themselves in science, in implementing four main practices: 'focusing in scientific discipline', 'innovating and problem solving', 'shaping new paradigms and models' and 'brokering science'. While 'focusing' and 'innovating' remain close to project management, 'shaping' and 'brokering' look more like entrepreneurial activities, shaping new horizons, reshaping boundaries between subfields and among organizations. External orientations to how they engage in different practices shapes PIs roles to articulate different worlds and to reshape the boundaries of organizations, knowledge and markets. Studying PIs' practices and their combinations advances our knowledge about their roles in managing the interplay between science policies and scientific agendas more effectively highlighting their role as scientific entrepreneurs.