Burnout is a syndrome characterized by emotional exhaustion, depersonalization, and reduced personal accomplishment that occurs in health-care professionals in response to chronic work-related stress. The percentage of US physicians experiencing high burnout increased during the COVID-19 pandemic compared to prepandemic, reaching 63%. Contributory factors include excessive workload, lack of control and autonomy, and loss of meaning, among others. Although strategies to manage burnout are multifaceted, involving individuals, institutions, and professional organizations, academic health centers should prioritize institutional factors in this postpandemic landscape. Broad system changes are necessary in order to address this epidemic that threatens the vitality of health care and academic medicine, with severe downstream effects on patients and learners.