As the complexity of health care delivery has increased, it has become essential for physicians to understand how individual practices relate to the larger system of care. It is within this context that the Accreditation Council for Graduate Medical Education (ACGME) and the American Board of Medical Specialties (ABMS) identified systems-based practice (SBP) as one of the six core competencies in which physicians must be proficient to deliver patient care that is safe and high in quality. SBP is challenging to define, incorporate into training and practice, and evaluate. Competency in SBP requires that physicians understand how patient care relates to the health care system as a whole and how to use the system to improve the quality and safety of patient care. Systems thinking is the cornerstone of SBP. Fostering the ability to recognize the contribution of the system is important for medical students, residents, and practicing physicians. However, current efforts in medical education focus on mastering knowledge of disease, diagnostic skills, and treatment at the level of the physician-patient interaction. As a result, there is a preoccupation with system components, while the system as a whole and its effect on the quality and safety of care remain invisible. To clarify the definition of SBP and to develop effective strategies for teaching and assessing SBP, it is necessary to provide a broad awareness of systems within a context of systems thinking. Patient safety is a good entry point into SBP because the concepts of safety, errors, and harm all place the individual, whether patient or provider, within the framework of a system.