Entrustable professional activities (EPAs) are measurable units of observable professional practice that can be entrusted to an unsupervised trainee. They were first introduced as a method of operationalizing competency-based medical education in graduate medical education. The American Association of Medical Colleges subsequently used EPAs to establish the core skills that medical students must be able to perform before they enter residency training. A recently published guide provides descriptions, guidelines, and rationale for implementing and assessing the core EPAs from an osteopathic approach. These osteopathically informed EPAs can allow schools to more appropriately assess a learner's whole-person approach to a patient, in alignment with the philosophy of the profession. As the single accreditation system for graduate medical education moves forward, it will be critical to integrate EPAs into osteopathic medical education to demonstrate entrustment of medical school graduates. The authors describe the collaborative process used to establish the osteopathic considerations added to EPAs and explores the challenges and opportunities for undergraduate osteopathic medical education.