After serving as commissioner of the US Food and Drug Administration (FDA) under President Obama, Robert M. Califf, MD, recently returned to the role, overseeing a critical federal agency that regulates food, drugs, therapeutics, and medical devices in the US. In a wide-ranging discussion with JAMA Deputy Editor Gregory Curfman, MD, Califf discusses COVID-19 vaccine modifications, the FDA’s approach to evaluating evidence, and efforts to combat health misinformation. Recorded April 26, 2022. Related Content: “Unfinished Business” Brings Robert Califf, MD, Back for a Second Stint as FDA Commissioner Q&A With FDA Commissioner Robert Califf