The US health care system is rapidly changing in an effort to deliver better care, improve health, and lower costs. While many of these changes positively impact the health of the country, they also add a lot of pressure to our current health care professionals. Excessive workloads and inefficiencies in documentation are commonplace, leading to high levels of burnout in our clinicians. In fact, burnout is nearly twice as prevalent among physicians as compared to US workers in other fields. Nurses are burnt out too, with 35% of hospital nurses experiencing high levels of emotional exhaustion. Clinician burnout should be a concern for everyone. Research shows that burnout leads to increased medical errors, decreased patient satisfaction, greater turnover and reduction in work effort, and higher health care costs. Despite decades of documenting the problem, information on effective interventions remains limited. In this National Academy of Medicine discussion paper, authors identify high-priority research principles that will help us gain further understanding of the factors and implications of clinician burnout and ways we can best support our health care workforce.