Problem-based learning (PBL) was first implemented by McMaster University medical school in 1969 as a radical, innovative, and alternative pathway to learning in medical education, thus setting a new educational trend. PBL has now spread widely across the globe and beyond the healthcare disciplines, and has prevailed for almost four decades. PBL is essentially a strategic learning system design, which combines several complementary educational principles for the delivery of instruction. PBL is specifically aimed at enhancing and optimizing the educational outcomes of learner-centered, collaborative, contextual, integrated, self-directed, and reflective learning. The design and delivery of instruction in PBL involve peer teaching and learning in small groups through the social construction of knowledge using a real-life problem case to trigger the learning process. Therefore, PBL represents a major shift in the educational paradigm from the traditional teacher-directed (teacher-centered) instruction to student-centered (learner-centered) learning. PBL is firmly underpinned by several educational theories, but problems are often encountered in practice that can affect learning outcomes. Educators contemplating implementing PBL in their institutions should have a clear understanding of its basic tenets, its practice and its philosophy, as well as the issues, challenges, and opportunities associated with its implementation. Special attention should be paid to the training and selection of PBL tutors who have a critical role in the PBL process. Furthermore, a significant change in the mindsets of both students and teachers are required for the successful implementation of PBL. Thus, effective training programs for students and teachers must precede its implementation. PBL is a highly resource-intensive learning strategy and the returns on investment (i.e. the actual versus expected learning outcomes) should be carefully and critically appraised in the decision-making process. Implementation of PBL can be a daunting task and will require detailed and careful planning, together with a significant commitment on the part of educators given the responsibility to implement PBL in an institution. PBL can offer a more holistic, value-added, and quality education to energize student learning in the healthcare professions in the 21st century. Successful implementation of PBL can therefore help to nurture in students the development of desired "habits of mind, behavior, and action" to become the competent, caring, and ethical healthcare professionals of the 21st century. Thus, PBL can contribute to the improvement of the healthcare of a nation by healthcare professionals, but we need to do it right.