The US Food and Drug Administration (FDA) is one of the largest and most important regulators of public health worldwide. Throughout its history, it has sought to build a reputation of decision-making based on science and evidence. However, shrinking trust in political institutions, growing political polarization, and a recent pandemic have confronted the FDA with unprecedent challenges. In light of these developments, we first provide an overview of the role that science and law have played across the development of the FDA. We then focus on notice and comment rulemaking and the guidance document process, which are broad policy and lawmaking tools used by the FDA, before assessing its narrower regulatory powers in the form of its drug and vaccine approval processes. After analyzing the FDA’s role during the COVID-19 pandemic, we provide an outlook for its future and offer a critical appraisal of where scholars have opportunities to advance knowledge.