The rapid dissemination and adoption of smart speakers has enabled substantial opportunities to improve human health. Just as the introduction of the mobile phone led to considerable health innovation, smart speaker computing systems carry several unique advantages that have the potential to catalyze new fields of health research, particularly in out-of-hospital environments. The recent rise and ubiquity of these smart computing systems holds significant potential for enhancing chronic disease management, enabling passive identification of unwitnessed medical emergencies, detecting subtle changes in human behavior and cognition, limiting isolation, and potentially allowing widespread, passive, remote monitoring of respiratory diseases that impact public health. There are 3 broad mechanisms for how a smart speaker can interact with a person to improve health. These include (1) as an intelligent conversational agent, (2) as a passive identifier of medically relevant diagnostic sounds, and (3) by active sensing using the device's internal hardware to measure physiologic parameters, such as with active sonar, radar, or computer vision. Each of these different modalities has specific clinical use cases, all of which need to be balanced against potential privacy concerns, equity concerns related to system access, and regulatory frameworks which have not yet been developed for this unique type of passive data collection.