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Despite ongoing efforts to improve working conditions, address well-being of faculty and students, and promote professionalism, many still feel the culture of academic medicine is problematic. Depression and burnout persist among physicians and trainees. The authors propose that culture change is so challenging in part because of an evolutionary construct known as the negativity bias that is reinforced serially in medical education. The negativity bias drives people to attend to and be more greatly affected by the negative aspects of experience. Some common teaching methods such as simulations, pimping, and instruction in clinical reasoning inadvertently reinforce the negativity bias and thereby enhance physicians’ focus on the negative. Here, the authors examine the concept of negativity bias in the context of academic medicine, arguing that culture is affected by serially emphasizing the inherent bias to recognize and remember the negative. They explore the potential role of practices rooted in positive psychology as powerful tools to counteract the negativity bias and aid in achieving desired culture change.