Problem-Based Learning (PBL) is known for engaging learners with active learning. As learners evolve, schools should adapt to enhance new teaching/learning strategies, all while ensuring the cultivation of graduates who align with the mission and goals of specific health professions, program accreditation requirements, and the institution. Although not a new curricular model, the tenets of PBL remain useful in any well-designed modern curriculum to embark on self-directed learning to develop lifelong learners. The combined effort and mindset change from the administration, the faculty, and the students is imperative to achieve a successful PBL program. The chapter introduces the design, construction, and operation of a PBL pre-clerkship curriculum and defines all stakeholders’ specific roles. More in-depth descriptions will be covered in subsequent chapters.