Problem-Based Learning (PBL) should adapt to the growing knowledge and clinical sophistication of medical students as they progress through the curriculum. At the University of Hawaii John A. Burns School of Medicine (JABSOM), PBL is the primary instructional method for pre-clerkship education. In this article, we share specific strategies to enhance the PBL content and process for early and advancing learners. This includes increased support for beginning students in the development of their self-directed learning skills. For advancing learners, we advocate increasing the clinical and emotional complexity of the cases, and integrating PBL with clinical skills education. Finally, we share a perspective on the placement of senior student tutors in the curriculum.