To date, formal training and assessment to enhance comfort with and management of uncertainty in clinical practice are lacking in many training programs. 1 A curriculum in Health Systems Science (HSS) can specifically acknowledge and address the uncertainty intrinsic to modern medical care and, in doing so, better prepare students for the transition to the clinical environment, the intrinsic complexity of the healthcare system, and the uncertainty of professional clinical practice. 3 To this effect, three core dimensions of uncertainty in clinical practice are described: the sources of uncertainty, the subjective nature of uncertainty, and responses to uncertainty. 3 The most common dimension in defining uncertainty is its source, which may stem from knowledge, relationships, and complex systems. 3 The cognitive impact these sources of uncertainty have in practitioners, in turn, influences their respective responses and actions. 3 Students ill-equipped to address uncertainty in the clinical environment can undergo cognitive dissonance, 4 diminished self-efficacy, and erosion of empathy. 5 Uncertainty can lead to maladaptive perfectionism and burnout. 6,7 The traditional emphasis on linear thinking in medical school can thwart creative problem-solving approaches, alternative perspectives, and the ability to calibrate for uncertainty 5—all of which are tools needed to thrive in today's clinical learning and working environment. Personal perspectives on uncertainty have been found to impact patient communication, 7 decision-making ability, 8 resource utilization, 7 and attitudes toward groups of patients. 9 Physicians' anxiety toward clinical uncertainty is associated with increased cost of care, as well as a reluctance to fully disclose information to patients. 7 Studies have even suggested that tolerance of uncertainty impacts students' willingness to work with underserved communities, and influences how providers address pain management during times of diagnostic ambiguity. 6,9,10 Intentional training in uncertainty is important not only because of the increasing complexity of healthcare and its associated systems but also because of the way access to information has changed personal relationships with uncertainty. Shortages of healthcare professionals, adequate access to personal protective equipment (PPE), and the urgent need for training clinical teams on infection control and prevention exemplified instances in which volatility, uncertainty, complexity, and ambiguity challenged CLEs and health systems together. 16 There was simply no time for clinical teams to step back and gain an understanding of the “big picture,” an overarching goal for systems thinking. 17 The pace of change and progress outstripped the ability to take a purposeful and analytic approach.