Purpose Changing an undergraduate medical curriculum is a recurring, high-stakes undertaking at medical schools. This study aimed to explore how people leading major curriculum changes conceived of the process of enacting change and the strategies they relied on to succeed in their efforts. Method The first author individually interviewed nine leaders who were leading or had led the most recent undergraduate curriculum change in one of the eight medical schools in the Netherlands. Interviews were between December 2015 and April 2016, using a semistructured interview format. Data analysis occurred concurrently with data collection, with themes being constructed inductively from the data. Results Leaders conceived of curriculum change as a dynamic, complex process. They described three major challenges they had to deal with while navigating this process: The large number of stakeholders championing a multitude of perspectives, dealing with resistance, and steering the change process. Additionally, strategies for addressing these challenges were described. The authors identified an underlying principle informing the work of these leaders: Being and remaining aware of emerging situations, and carefully constructing strategies for ensuring that the intended outcomes were reached and contributed to the progress of the change process. Discussion This empirical, descriptive study enriches the understanding of how institutional leaders navigate the complexities of major medical curriculum changes. The insights serve as a foundation for training and coaching future change leaders. To broaden the understanding of curriculum change processes, future studies could investigate the processes through alternative stakeholder perspectives.