The theme of this thesis is how learning takes place in problem-based learning (PBL). The objectives of the studies presented were to gain insight into what and how students learn in all the phases of the PBL cycle, as well as to identify relationships between the learning activities of students (that is: what they know, say, and do) with their learning outcomes. Much of the research on PBL has been focused on effects of this approach on curricular outcomes (Dochy, Segers, Van den Bossche, & Gijbels, 2003; Schmidt & Moust, 2000). However, answers to the question of how the process of PBL produces these outcomes are still few. To contribute to our understanding of the nature of learning in PBL, I applied different methodologies to analyze and describe the PBL process in a naturalistic setting.